Hits 1 - 10 (out of 6928 matching entities) [14344 mentions] (45 ms):
1. chronic myeloid leukemias

11634 articles, score 3843.965

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • Chronic Myeloid Leukemia (CML) originates in a leukemic stem cell that resides in the bone marrow microenvironment, where they coexist with cellular and non-cellular elements. The vascular microenvironment has been identified as an important element in CML development since an increase in the vascularization has been suggested to be related with poor prognosis; also, using murine models, it has been reported that bone marrow endothelium can regulate the quiescence and proliferation of leukemic stem and progenitor cells. This observation, however, has not been evaluated in primary human cells. In this report, we used a co-culture of primitive (progenitor and stem) CML cells with endothelial colony forming cells (ECFC) as an in vitro model to evaluate the effects of the vascular microenvironment in the leukemic hematopoiesis. Our results show that this interaction allows the in vitro maintenance of primitive CML cells through an inflammatory microenvironment able to regulate the proliferation of progenitor cells and the permanence in a quiescent state of leukemic stem cells.
    Cell Contact with Endothelial Cells Favors the In Vitro Maintenance of Human Chronic Myeloid Leukemia Stem and Progenitor Cells.
    International journal of molecular sciences, Sep 2022 [PubMed 36142235]
  • Chronic myeloid leukemia (CML) most commonly presents in chronic phase. Blast crisis in CML is usually of myeloid phenotype, whereas among lymphoid lineage, B-cell lymphoblastic crisis is common. T lymphoblastic crisis is rare with near early T-cell precursor (ETP) immunophenotype being exceedingly rare and very little is known about its characteristics, treatment, and prognosis. Blast crisis can occur in extramedullary sites with lymph node being the most common site. CML is also less investigated and studied in pregnancy as it is considered a disease of older adults. We report a rare case of CML presenting in extramedullary site (lymph node) as extramedullary T-cell lymphoblastic crisis of near ETP immunophenotype in a young pregnant female, which was diagnosed on fine-needle aspiration cytology in combination with flow cytometry.
    Extramedullary early T-cell lymphoblastic crisis in a young pregnant chronic myeloid leukemia patient: Diagnosis with fine-needle aspiration cytology and flow cytometry.
    Diagnostic cytopathology, Jul 2022 [PubMed 35170252]
  • T cell dysfunction is a common characteristic of patients with myeloid leukemia and is closely related to clinical efficacy and prognosis. In order to clarify the mechanisms leading to the T cell dysfunction, we characterized the gene expression profile of T cells from chronic myelogenous leukemia (CML) patients by microarray analysis and investigated the related regulating pathway. We employed gene expression profiling, bioinformatics and real-time quantitative reverse transcription PCR (RT-qPCR) to detect genes differentially expressed in CML patients versus healthy donors. T cells from CML patients was significantly lower than that in healthy donors. may be involved in regulating T cell dysfunction in CML patients in the form of a transcriptional regulatory network. These findings may provide potential targets for tyrosine kinase inhibitors in combination with other targeted immunotherapies .
    expression in T cells from chronic myeloid leukemia patients.
    Hematology (Amsterdam, Netherlands), Dec 2022 [PubMed 35544467]

2. acute myeloid leukemias

3384 articles, score 1007.065

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • Invasive fungal sinusitis (IFS) in patients with active or recent COVID-19 have been reported throughout the world. The primary purpose of the systematic review is to describe factors associated with IFS in patients with COVID-19. The goal of the case series was to also characterize these factors in addition to evaluating the incidence of IFS at our institution after the onset of the pandemic. A systematic review using the preferred reporting in systematic reviews and meta-analyses (PRISMA) framework identified publications of IFS cases associated with COVID-19 (IFSAC). Search terms were "COVID-19," "invasive," "fungal," and "sinusitis." IFS cases were evaluated for COVID-19 status, fungal etiology, comorbidities, treatment, and outcome. A case series of patients at our center with IFS between December 1, 2018 to March 31, 2020 ("pre-covid") and April 1, 2020 to August 1, 2021 ("post-covid") was also performed with the above parameters. Fourteen studies totaling 206 cases of IFSAC were identified. Most cases came from India (140/206, 68.0%), followed by Egypt (62/206, 30.1%), and North America (4/206, 1.9%). Diabetes was the most common comorbidity (151/206, 73.3%). Recent or prolonged steroid use was noted in 65.0% of cases (134/206). In our series, five pre-covid and four post-covid cases were identified. One had recent COVID-19 infection. Acute myeloid leukemia was the most common pre-covid comorbidity (3/5, 60.0%). Diabetes was the most frequent post-covid comorbidity (2/4, 50.0%). Chronic steroid usage was noted in two pre-covid and one post-covid cases. Diabetes and steroid use are common factors in reported cases of IFSAC. IFS incidence in our case series did not change appreciably after the onset of the pandemic.Level of Evidence: 4.
    Factors associated with invasive fungal sinusitis in patients with COVID-19: A systematic review and single-center case series.
    Laryngoscope investigative otolaryngology, Jun 2022 [PubMed 35942423]
  • Both chronic myeloid leukemia and acute myeloid leukemia evade the immune response during their development and disease progression. As myeloid leukemia cells modify their bone marrow microenvironment, they lead to dysfunction of cytotoxic cells, such as CD8+ T cells or NK cells, simultaneously promoting development of immunosuppressive regulatory T cells and suppressive myeloid cells. This facilitates disease progression, spreading of leukemic blasts outside the bone marrow niche and therapy resistance. The following review focuses on main immunosuppressive features of myeloid leukemias. Firstly, factors derived directly from leukemic cells - inhibitory receptors, soluble factors and extracellular vesicles, are described. Further, we outline function, properties and origin of main immunosuppressive cells - regulatory T cells, myeloid derived suppressor cells and macrophages. Finally, we analyze interplay between recovery of effector immunity and therapeutic modalities, such as tyrosine kinase inhibitors and chemotherapy.
    Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias.
    Cancers, Mar 2021 [PubMed 33801964]
  • The use of molecular genetic biomarkers is rapidly advancing to aid diagnosis, prognosis, and clinical management of hematological disorders. We have implemented a next-generation sequencing (NGS) assay for detection of genetic variants and fusions as a frontline test for patients suspected with myeloid malignancy. In this study, we summarize the findings and assess the clinical impact in the first 1613 patients tested. All patients were assessed using NGS based Oncomine Myeloid Research Assay (ThermoFisher) including 40 genes (17 full genes and 23 genes with clinically relevant "hotspot" regions), along with a panel of 29 fusion driver genes (including over fusion 600 partners). Among 1613 patients with suspected myeloid malignancy, 43% patients harbored at least one clinically relevant variant: 91% (90/100) in acute myeloid leukemia patients, 71.7% (160/223) in myelodysplastic syndrome (MDS), 77.5% (308/397) in myeloproliferative neoplasm (MPN), 83% (34/41) in MPN/MDS, and 100% (40/40) in chronic myeloid leukemia patients. Comparison of NGS and cytogenetics results revealed a high degree of concordance in gene fusion detection. Our findings demonstrate clinical utility and feasibility of integrating a NGS-based gene mutation and fusion testing assay as a frontline diagnostic test in a large reported cohort of patients with suspected myeloid malignancy, in a clinical laboratory setting. Overlap with cytogenetic test results provides opportunity for testing reduction and streamlining.
    Clinical Utility of Implementing a Frontline NGS-Based DNA and RNA Fusion Panel Test for Patients with Suspected Myeloid Malignancies.
    Molecular diagnosis & therapy, May 2022 [PubMed 35381971]

3. leukemias

3160 articles, score 821.662

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • The hematopoietic stem cells (HSCs) are sensitive to radiation. Chronic exposure to low dose rate (LDR) radiation at 20 mGy/day results in a decrease in the number of HSCs and an increase of leukemia. In this study, the proliferative capacities of ex vivo HSCs, exposed to 20 mGy/day of gamma-rays for 20 days, were compared with those of in vivo HSCs from similarly whole-body-irradiated mice. Radiation suppressed the growth of the ex vivo HSCs after Day 16 of irradiation and until Day 7 post-exposure. Almost all types of cells, particularly multipotent progenitors, common myeloid progenitors, granulocytes and macrophages, were significantly reduced in number at Day 20 of irradiation and Day 7 post-exposure in culture. HSCs and multipotent progenitors irradiated in vivo, however, decreased transiently and recovered by Day 7 post-exposure. These findings suggest that the microenvironment in vivo protects HSCs from the effects of LDR radiation.
    COMPARISON OF THE PROLIFERATIVE RESPONSES OF HEMATOPOIETIC STEM CELLS EXPOSED TO LOW DOSE RATE RADIATION IN VIVO AND EX VIVO.
    Radiation protection dosimetry, Sep 2022 [PubMed 36083736]
  • Tyrosine kinase inhibitors (TKIs) improve outcomes for pediatric malignancies characterized by specific gene rearrangements and mutations; however, little is known about the long-term impact of TKI exposure. Our objective was to assess the incidence and type of late-onset TKI-related toxicities in children with chronic myeloid leukemia (CML). We reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21 years of age and prescribed one or more TKIs. Patients treated with stem cell transplant were excluded. Outcomes were captured beginning at 1 year after CML diagnosis. Outcome incidence was described overall and stratified by TKI exposure during the data-capture period. Twenty-two eligible TKI-exposed patients with CML were identified. The median follow-up was 6.0 years (range: 2.2-14.3). All pericardial (n = 3) or pleural (n = 3) effusion outcomes occurred in patients treated with TKIs during the data-capture period. Other outcomes included hypertension (n = 2), ectopy on electrocardiogram (n = 2), and gastrointestinal bleed (n = 1). All outcomes were graded as mild to moderate: some resulted in a temporary discontinuation of TKI, but none led to a change in TKI. No differences were noted in outcome incidence by type of TKI exposure. TKIs have substantially improved prognosis for subsets of childhood leukemia, but there are limited long-term data to inform exposure-based risk for late-onset complications and screening. Our results suggest that TKI-exposed survivors may be at risk for long-term outcomes that extend well into survivorship.
    Distribution and frequency of tyrosine kinase inhibitor-associated long-term complications in children with chronic myeloid leukemia.
    Pediatric blood & cancer, Sep 2022 [PubMed 35593027]
  • The idea of functional non-coding RNAs is taking precedence over the previous notion which believed that they only comprise the auxiliary and junk material of the genome. Newer technologies and studies have proven their importance in regulating and affecting several cellular processes. One such area of research wherein their importance has started to take light is in cancer research, particularly leukemia. Myeloid leukemia is a blood malignancy birthed from mutations in hematopoiesis that disable myeloid progenitor cells from proper differentiation. This review will compile the most recent findings regarding the effects of these regulatory non-coding RNAs on the two types of myeloid leukemia. In particular, the effects of circular RNAs, micro RNAs and long non-coding RNAs, on the pathogenesis and proliferation of Acute and Chronic myeloid leukemia will be revealed in a molecular, cellular and prognostic light. The mechanisms of proliferation, gene-to-gene interactions and possible therapeutic effects will also be discussed. Finally, an understanding of the overall "goodness" and "badness" of these non-coding RNAs will be summarised. This review hopes to provide a platform for easy access to data regarding the current non-coding RNAs in myeloid leukemia, for faster and easier research. Finally, the review will summarize a few key players that have protagonistic and antagonistic functions, and those that regulate multiple pathways in leukemia simultaneously.
    Non-coding RNAs: are they the protagonist or antagonist in the regulation of leukemia?
    American journal of translational research, 2022 [PubMed 35422954]

4. imatinib

3817 articles, score 778.971

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • The development and approval of the tyrosine kinase inhibitor imatinib in 2001 has heralded the advance of directed therapy options. Today, an armamentarium of targeted therapeutics is available and enables the use of precision medicine in non-solid cancer. Precision medicine is guided by the detection of tumor-specific and targetable characteristics. These include pathogenic fusions and/or mutations, dependency on specific signaling pathways, and the expression of certain cell surface markers. Within the first part, we review approved targeted therapies for the compound classes of small molecule inhibitors, antibody-based therapies and cellular therapies. Particular consideration is given to the underlying pathobiology and the respective mechanism of action. The second part emphasizes on how biomarkers, whether they are of diagnostic, prognostic, or predictive relevance, are indispensable tools to guide therapy choice and management in precision medicine. Finally, the examples of acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia illustrate how integration of these biomarkers helps to tailor therapy.
    Precision Medicine in Therapy of Non-solid Cancer.
    Handbook of experimental pharmacology, Aug 2022 [PubMed 35989345]
  • Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic phase chronic myeloid leukemia (CP-CML) patients who had achieved a sustained deep molecular response. Based on the results of discontinuation trials, recommendations regarding patient selection for a treatment-free remission (TFR) attempt had been proposed. The aims of this study were to evaluate the rate of patients eligible for TKI discontinuation and molecular recurrence-free survival (MRFS) after stop according to recommendations. Over a 10-year period, newly diagnosed CP-CML patients and treated with first-line TKI in the nine French participating centers were included. Eligibility to treatment discontinuation and MRFS were analyzed and compared according to selection criteria defined by recommendations and first-line treatments. From January 2006 to December 2015, 398 patients were considered. Among them, 73% and 27% of patients received imatinib or either second or third generation tyrosine kinase inhibitors as frontline treatment, respectively. Considering the selection criteria defined by recommendations, up to 55% of the patients were selected as optimal candidates for treatment discontinuation. Overall 95/398 (24%) discontinued treatment. MRFS was 51.8% [95% CI 41.41-62.19] at 2 years and 43.8% [31.45-56.15] at 5 years. Patients receiving frontline second-generation TKI and fulfilling the eligibility criteria suggested by recommendations had the lowest probability of molecular relapse after TKI stop when compare to others. One third of CP-CML patients treated with TKI frontline fulfilled the selection criteria suggested by European LeukemiaNet TFR recommendations. Meeting selection criteria and second-generation TKI frontline were associated with the highest MRFS.
    Relevance of treatment-free remission recommendations in chronic phase chronic leukemia patients treated with frontline tyrosine kinase inhibitors.
    Cancer medicine, Jun 2021 [PubMed 33988316]
  • We evaluated the feasibility of existing risk assessment tools for chronic myeloid leukemia (CML) in children. Fifty-five patients with newly diagnosed CML between 1996 and 2019 were included. Forty-nine patients presented in chronic phase, thirty-six of whom were treated with upfront tyrosine kinase inhibitor (CP-TKI group); one presented in accelerated phase and four in blastic phase. Treatment, survival, responses, and tolerance were evaluated. All patients in the CP-TKI group received imatinib as their first TKI treatment. The 10-year overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) of TKI-treated group was 97%, 91.4%, and 72.3%, respectively. At 60 months, the rates of major molecular response were 81.2% and deep molecular response was 67.5%. The EUTOS long-term survival (ELTS) risk grouping did not predict OS, PFS, or EFS. The IMAFAIL risk groups were correlated with the risk of imatinib failure. Further studies are required to modify the existing risk assessment tools for children.
    Outcome prediction of chronic myeloid leukemia (CML) in children.
    Annals of hematology, Aug 2022 [PubMed 35641639]

5. BCR-ABL

1992 articles, score 368.934

Entity Information

Molecular Interaction Network

Not available

Enriched GO Terms

Not available

Abstracts

  • Chronic myeloid leukemia (CML) is a myeloproliferative disease that results from the BCR-ABL gene-induced transformation of a primitive hematopoietic cell. This disease has been extensively studied, and, as a result, a very effective therapy has been developed: the tyrosine kinase inhibitors. Although, there is a significant knowledge about the intrinsic biology of CML cells, alterations in their bone marrow microenvironment are not yet completely understood. In this concise review, we summarized recent findings on the composition and function of the bone marrow microenvironment in CML, and their importance in the progression of the disease and treatment resistance.
    Understanding the hematopoietic microenvironment in chronic myeloid leukemia: A concise review.
    Current research in translational medicine, Jul 2021 [PubMed 33962119]
  • Beginning with imatinib and now spanning 6 oral, highly active, and mostly safe agents, the development of specific targeted therapy for patients with chronic myeloid leukemia (CML) has created a new world featuring chronic maintenance chemotherapy for all treated as such, treatment-free remission, and functional cure after prolonged deep remission in a subset. As a result comes a necessary shift in focus from acute to chronic toxicity, increasing attention to patient comorbidities, and critical thinking around specific adverse events such as metabolic, cardiovascular, and cardiopulmonary effects, which vary from agent to agent. This review aims to pull together the state of the art of managing the "C" in CML-a chronic myeloproliferative neoplasm treated at present over many years with oral BCR-ABL-targeted agents in a population whose overall health can be complex and potentially affected by disease and therapy-and determine how we can better manage a highly treatable and increasingly curable cancer.
    Lifelong TKI therapy: how to manage cardiovascular and other risks.
    Hematology. American Society of Hematology. Education Program, Dec 2021 [PubMed 34889360]
  • To estimate the resource gap in the polymerase chain reaction (PCR) monitoring for patients with chronic myeloid leukemia (CML) in low- and middle-income countries (LMICs). system. We included costs of GeneXpert® instruments, uninterrupted power supplies, warranties, calibration kits, test cartridges, and shipping. We calculated the country-specific monetary gap in PCR monitoring, stratified by country priority defined as the availability of tyrosine kinase inhibitors (TKIs) through The Max Foundation initiatives. The 5-year gap in PCR monitoring was $29.1 million across all countries, 22% ($6.4 million) in countries with all five TKIs available, 20% ($5.7 million) in countries with four TKIs available, 50% ($14.5 million) in countries with three TKIs available, 8% ($2.2 million) in countries with two TKIs available, and 1% ($0.3 million) in countries with one TKI available. The gap was highest in South Asia (52%; $15.1 million) and lowest in Latin America (6%; $1.9 million). Excluding labor costs, the bulk of the resource needs (86%; $25.2 million) were for procurement of BCR-ABL cartridges. Removing the 5-year gap in PCR monitoring capacity for CML in LMICs will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research. Development of streamlined monitoring guidelines for resource-limited countries should be considered.
    Analysis of the gap in PCR monitoring availability for patients with chronic myeloid leukemia in 60 low- and middle-income countries.
    Cost effectiveness and resource allocation : C/E, Mar 2021 [PubMed 33712039]

6. lymphoblastic leukemia

1541 articles, score 341.765

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • Few therapeutic options are available for patients with acute myeloid or lymphoblastic leukemia (AML/ALL) relapsing after a second allogeneic stem cell transplantation (alloSCT2). In selected patients a third allogeneic stem cell transplantation (alloSCT3) has been used, but no detailed analysis is available so far. The European Society for Blood and Marrow Transplantation (EBMT) registry was screened for patients with acute leukemia (AL) receiving alloSCT3 from an identical or alternative donor to treat AL in either haematological relapse or disease persistence after alloSCT2 between 2001 and 2018. Feasibility, efficacy, outcome, and risk factors of this approach were analyzed retrospectively. Forty-five patients (median age, 37 years, range 12-71) with AML (n=34) or ALL (n=11) were identified. Eleven patients received alloSCT3 in complete remission (CR), 34 had active disease. Fifteen patients were transplanted from the same donor at all three transplants, 30 patients had at least 2 different donors. Between alloSCT2 and alloSCT3, the donor was changed in 25 patients. After alloSCT3, 38 patients engrafted, and 26 achieved CR or CR with incomplete hematological reconstitution (CRi). Acute graft-versus-host disease (GvHD) grade II-IV was observed in 19%, chronic GvHD occurred in 13%. After 1-year, cumulative incidences of leukemia relapse and non-relapse mortality were 47% and 42%, respectively. Median progression free and overall survival (PFS/OS) from alloSCT3 were 2.5 and 4 months, respectively, 1-year PFS and OS were 11% and 20%,. Outcome was improved in patients with at least one donor change (1-year PFS/OS: 17%/30%), further factors for better outcome included an unrelated donor for alloSCT3, Karnofsky performance score >80, and more recent year of alloSCT3. Only patients with AML achieved >1 year OS. In conclusion, results after a third alloSCT are poor, limiting this procedure to few, highly selected patients. Recurrent relapses of acute leukemia after alloSCT remain an unmet therapeutic need.
    Feasibility and Outcomes of a Third Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
    Transplantation and cellular therapy, May 2021 [PubMed 33965180]
  • Effectual cell-to-cell communication is essential to the development and differentiation of organisms, the preservation of tissue tasks, and the synchronization of their different physiological actions, but also to the proliferation and metastasis of tumor cells. Tunneling nanotubes (TNTs) are membrane-enclosed tubular connections between cells that carry a multiplicity of cellular loads, such as exosomes, non-coding RNAs, mitochondria, and proteins, and they have been identified as the main participants in healthy and tumoral cell communication. TNTs have been described in numerous tumors in in vitro, ex vivo, and in vivo models favoring the onset and progression of tumors. Tumor cells utilize TNT-like membranous channels to transfer information between themselves or with the tumoral milieu. As a result, tumor cells attain novel capabilities, such as the increased capacity of metastasis, metabolic plasticity, angiogenic aptitude, and chemoresistance, promoting tumor severity. Here, we review the morphological and operational characteristics of TNTs and their influence on hematologic malignancies' progression and resistance to therapies, focusing on acute and chronic myeloid and acute lymphoid leukemia. Finally, we examine the prospects and challenges for TNTs as a therapeutic approach for hematologic diseases by examining the development of efficient and safe drugs targeting TNTs.
    Specialized Intercellular Communications via Tunnelling Nanotubes in Acute and Chronic Leukemia.
    Cancers, Jan 2022 [PubMed 35158927]
  • Lineage infidelity is characteristic of mixed phenotype acute leukemia and is also seen in blast phase of chronic myeloid leukemia (CML), myeloid/lymphoid neoplasia with eosinophilia and gene rearrangements, and subtypes of acute myeloid leukemia. Driver genetic events often occur in multipotent progenitor cells in myeloid neoplasms, suggesting that multilineage output may be more common than appreciated. This phenomenon is not well studied in myelodysplastic syndrome (MDS) and non-CML myeloproliferative neoplasms (MPN). We systematically evaluated phenotypic lineage infidelity by reviewing bone marrow pathology and flow cytometry (FC) studies of 1262 consecutive patients with a diagnosis of MDS and/or non-CML MPN. We assessed B- and T-cells in these patients by FC. When abnormal B-lymphoblast (ABLB) populations were detected, we additionally evaluated immature B-cells using a high sensitivity FC assay for B-lymphoblastic leukemia/lymphoma (B-ALL). We identified 9 patients (7 MDS, 7/713, 1%; 2 non-CML MPN, 2/312, 0.6%; 0 in MDS/MPN) with low-level ABLB populations (0.012%-3.6% of WBCs in marrow) with abnormal immunophenotypes. Genetic studies on flow sorted cell populations confirmed that some ABLB populations were clonally related to myeloid blasts (4/6, 67%). On follow-up, ABLB populations in 8/9 patients remained stable or disappeared. Only 1 case progressed to B-ALL. These findings demonstrate that phenotypically detectable abnormal immature B lineage output occurs in MDS and non-CML MPN, albeit rarely. While presence of ABLB does not necessarily reflect blast crisis, the underlying disease biology of our findings may ultimately be relevant to patient management and warrants further investigation.
    Abnormal B-lymphoblasts in myelodysplastic syndromes and myeloproliferative neoplasms other than chronic myeloid leukemia.
    Cytometry. Part B, Clinical cytometry, Dec 2021 [PubMed 34897961]

7. myelodysplastic syndromes

1222 articles, score 336.653

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • The use of molecular genetic biomarkers is rapidly advancing to aid diagnosis, prognosis, and clinical management of hematological disorders. We have implemented a next-generation sequencing (NGS) assay for detection of genetic variants and fusions as a frontline test for patients suspected with myeloid malignancy. In this study, we summarize the findings and assess the clinical impact in the first 1613 patients tested. All patients were assessed using NGS based Oncomine Myeloid Research Assay (ThermoFisher) including 40 genes (17 full genes and 23 genes with clinically relevant "hotspot" regions), along with a panel of 29 fusion driver genes (including over fusion 600 partners). Among 1613 patients with suspected myeloid malignancy, 43% patients harbored at least one clinically relevant variant: 91% (90/100) in acute myeloid leukemia patients, 71.7% (160/223) in myelodysplastic syndrome (MDS), 77.5% (308/397) in myeloproliferative neoplasm (MPN), 83% (34/41) in MPN/MDS, and 100% (40/40) in chronic myeloid leukemia patients. Comparison of NGS and cytogenetics results revealed a high degree of concordance in gene fusion detection. Our findings demonstrate clinical utility and feasibility of integrating a NGS-based gene mutation and fusion testing assay as a frontline diagnostic test in a large reported cohort of patients with suspected myeloid malignancy, in a clinical laboratory setting. Overlap with cytogenetic test results provides opportunity for testing reduction and streamlining.
    Clinical Utility of Implementing a Frontline NGS-Based DNA and RNA Fusion Panel Test for Patients with Suspected Myeloid Malignancies.
    Molecular diagnosis & therapy, May 2022 [PubMed 35381971]
  • Myelodysplastic syndromes (MDSs) are clonal hematopoietic diseases of the elderly, characterized by chronic cytopenia, ineffective and dysplastic hematopoiesis, recurrent genetic abnormalities and increased risk of progression to acute myeloid leukemia. Diagnosis on a complete blood count (CBC) can be challenging due to numerous other non-neoplastic causes of cytopenias. New generations of hematology analyzers provide cell population data (CPD) that can be exploited to reliably detect MDSs from a routine CBC. In this review, we first describe the different technologies used to obtain CPD. We then give an overview of the currently available data regarding the performance of CPD for each lineage in the diagnostic workup of MDSs. Adequate exploitation of CPD can yield very strong diagnostic performances allowing for faster diagnosis and reduction of time-consuming slide reviews in the hematology laboratory.
    Automated Detection of Dysplasia: Data Mining from Our Hematology Analyzers.
    Diagnostics (Basel, Switzerland), Jun 2022 [PubMed 35885462]
  • Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm development. This review analyzes the main features of MDSCs and MSCs in myeloid malignancies. The number of MDSCs is elevated in myeloid malignancies exhibiting high immunosuppressive capacities, whereas MSCs, in addition to their immunosuppression contribution, regulate myeloid leukemia cell proliferation, apoptosis, and chemotherapy resistance. Moreover, MSCs may promote MDSC expansion, which may mutually contribute to the creation of an immuno-tolerant neoplasm microenvironment. Understanding the implication of MDSCs and MSCs in myeloid malignancies may favor their potential use in immunotherapeutic strategies.
    Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies.
    Journal of clinical medicine, Jun 2021 [PubMed 34202907]

8. BCR-ABL1

852 articles, score 327.548

Entity Information

Molecular Interaction Network

Not available

Enriched GO Terms

Not available

Abstracts

  • Cardiovascular (CV) risk mitigation is an important consideration in the management of chronic myeloid leukemia (CML) patients. Although BCR-ABL1 inhibition by tyrosine kinase inhibitors (TKI) has led to a significant improvement in prognosis, the majority of CML patients will require indefinite TKI therapy. Given the success of therapy, there has been a shift in focus to include CV care as part of routine patient management. To optimize outcomes, both patient-specific comorbidities and a detailed understanding of the cardiotoxicity safety profiles imparted by each TKI should be considered during agent selection. Clinicians face the challenge of early detection and management of these cardiotoxicities while balancing the risk-benefit ratios of maintaining life-saving cancer therapy. Advanced practitioners play a critical role in CML patient management that extends to the recognition and management of TKI-associated side effects. They should be cognizant of the potential for TKI-associated cardiotoxicities along with appropriate baseline risk assessments, active surveillance, and mitigation strategies as part of a collaborative team effort with cardio-oncologists.
    Cardiovascular Adverse Events and Mitigation Strategies for Chronic Myeloid Leukemia Patients Receiving Tyrosine Kinase Inhibitor Therapy.
    Journal of the advanced practitioner in oncology, Mar 2022 [PubMed 35369400]
  • Precise quantification of molecular targets in a biological sample across a wide dynamic range is a key requirement in many diagnostic procedures, such as monitoring response to therapy or detection of measurable residual disease. State of the art digital PCR assays provide for a dynamic range of four orders of magnitude. However digital assays are complex and require sophisticated microfluidic tools. Here we present an assay format that enables ultra-precise quantification of RNA targets in a single measurement across a dynamic range of more than six orders of magnitude. The approach is based on hydrogel beads that provide for microfluidic free compartmentalization of the sample as they are used as nanoreactors for reverse transcription, PCR amplification and combined real time and digital detection of gene transcripts. We have applied these nanoreactor beads for establishing an assay for the detection and quantification of BCR-ABL1 fusion transcripts. The assay has been characterized for its precision and linear dynamic range. A comparison of the new method against conventional real time RT-PCR analysis (reference method) with clinical samples from patients with chronic myeloid leukemia (CML) revealed excellent concordance with Pearsons correlation coefficient of 0.983 and slope of 1.08.
    Ultra-precise quantification of mRNA targets across a broad dynamic range with nanoreactor beads.
    PloS one, 2021 [PubMed 33735175]
  • mutations confer resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Olverembatinib is a new potent BCR-ABL1 TKI with preclinical activity against T315I-mutated CML. In phase 1/2 studies, we explored the safety and efficacy of olverembatinib in Chinese adults with TKI-resistant CML in the chronic phase (CML-CP) and accelerated phase (CML-AP). In the phase 1 study, olverembatinib was orally administered once every other day in 28-day cycles at 11 dose cohorts ranging from 1 to 60 mg, and we evaluated the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics of olverembatinib. In the phase 2 studies, olverembatinib was administered at the RP2D of 40 mg orally on alternate days for 28-day cycles. The primary outcome measure is major cytogenetic response (MCyR) and major hematologic response by the end of Cycle 12 in CML-CP and CML-AP, respectively. Fine and Gray's hazard models were used to identify covariates associated with responses. were 47.4%, 47.4%, 44.7%, 39.3%, and 32.1%, respectively. In multivariate analyses, baseline BCR-ABL1 mutation status was significantly associated with cytogenetic and molecular responses. Common treatment-related adverse events included skin hyperpigmentation, hypertriglyceridemia, proteinuria, and severe thrombocytopenia. Olverembatinib was well tolerated, with significant antileukemic activity in adults with TKI-resistant CML-CP and CML-AP, especially those with the T315I mutation. The phase 1 trial is registered at CTR20220566, and the two single-arm, open-label phase 2 studies are registered at ClinicalTrials.gov: NCT03883087 (CML-CP) and NCT03883100 (CML-AP).
    Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial.
    Journal of hematology & oncology, Aug 2022 [PubMed 35982483]

9. hematologic malignancies

1074 articles, score 281.726

Entity Information

Molecular Interaction Network

Not available

Enriched GO Terms

Not available

Abstracts

  • Effectual cell-to-cell communication is essential to the development and differentiation of organisms, the preservation of tissue tasks, and the synchronization of their different physiological actions, but also to the proliferation and metastasis of tumor cells. Tunneling nanotubes (TNTs) are membrane-enclosed tubular connections between cells that carry a multiplicity of cellular loads, such as exosomes, non-coding RNAs, mitochondria, and proteins, and they have been identified as the main participants in healthy and tumoral cell communication. TNTs have been described in numerous tumors in in vitro, ex vivo, and in vivo models favoring the onset and progression of tumors. Tumor cells utilize TNT-like membranous channels to transfer information between themselves or with the tumoral milieu. As a result, tumor cells attain novel capabilities, such as the increased capacity of metastasis, metabolic plasticity, angiogenic aptitude, and chemoresistance, promoting tumor severity. Here, we review the morphological and operational characteristics of TNTs and their influence on hematologic malignancies' progression and resistance to therapies, focusing on acute and chronic myeloid and acute lymphoid leukemia. Finally, we examine the prospects and challenges for TNTs as a therapeutic approach for hematologic diseases by examining the development of efficient and safe drugs targeting TNTs.
    Specialized Intercellular Communications via Tunnelling Nanotubes in Acute and Chronic Leukemia.
    Cancers, Jan 2022 [PubMed 35158927]
  • Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2 serology were more frequently male (p = 0.027) and active workers (p = 0.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population.
    The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population.
    Cancer medicine, Sep 2021 [PubMed 34464516]
  • Mutation detection is increasingly used for the management of hematological malignancies. Prior whole transcriptome and whole exome sequencing studies using total RNA and DNA identified diverse mutation types in cancer-related genes associated with treatment failure in patients with chronic myeloid leukemia. Variants included single-nucleotide variants and small insertions/deletions, plus fusion transcripts and partial or whole gene deletions. The hypothesis that all of these mutation types could be detected by a single cost-effective hybridization capture next-generation sequencing method using total RNA was assessed. A method was developed that targeted 130 genes relevant for myeloid and lymphoid leukemia. Retrospective samples with 121 precharacterized variants were tested using total RNA and/or DNA. Concordance of detection of precharacterized variants using RNA or DNA was 96%, whereas the enhanced sensitivity identified additional variants. Comparison between 24 matched DNA and RNA samples demonstrated 95.3% of 170 variants detectable using DNA were detected using RNA, including all but one variant predicted to activate nonsense-mediated decay. RNA identified an additional 10 variants, including fusion transcripts. Furthermore, the true effect of splice variants on RNA splicing was only evident using RNA. In conclusion, capture sequencing using total RNA alone is suitable for detecting a range of variants relevant in chronic myeloid leukemia and may be more broadly applied to other hematological malignancies where diverse variant types define risk groups.
    RNA-Based Targeted Gene Sequencing Improves the Diagnostic Yield of Mutant Detection in Chronic Myeloid Leukemia.
    The Journal of molecular diagnostics : JMD, Jul 2022 [PubMed 35550185]

10. dasatinib

1062 articles, score 264.736

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • To report a case of bilateral vision loss as the primary presenting symptom of chronic myeloid leukemia in a young adult. The 28-year-old male patient presented to clinic with visual acuity of 20/200 in both eyes after several months of episodic bilateral vision loss. Intraretinal and pre-retinal hemorrhages were appreciated, as well as Roth spots and peripheral neovascularization. Initial lab findings were consistent with a diagnosis of acute myeloid leukemia, later, upon bone marrow examination, the diagnosis was edited to chronic myeloid leukemia. Dasatinib therapy resulted in a complete hematologic resolution after six weeks. After intravitreal injections of bevacizumab in both eyes, visual acuity improved to 20/25 in the right eye and 20/20 in the left eye. After review, this is one of only a few reported cases of bilateral blurry vision as the primary presenting symptom of chronic myeloid leukemia in a young adult. Because visual disturbances occur more frequently in acute myeloid leukemia, and lab results may be inconclusive, careful consideration should be given to differentiate myelogenous leukemias, as the acute and chronic subtypes may present similarly.
    Bilateral vision loss as initial presentation of chronic myeloid leukemia in a young adult: A case report and review of the literature.
    American journal of ophthalmology case reports, Jun 2022 [PubMed 35602313]
  • In this review, we first present a case of chronic myeloid leukemia with acute psychosis, and then we will discuss the incidence of cancer in patients with psychotic disorders, the manifestations of new-onset psychosis, and the prevalence of preexisting psychosis in cancer patients, coupled with their impact on the treatment, diagnosis, and prognosis of cancer. This was a case that presented with acute psychosis and was found to have an elevated white blood cell count upon admission to an inpatient psychiatric unit. He was diagnosed with chronic myeloid leukemia and successfully managed with imatinib/dasatinib therapy. Psychiatrically, he was stabilized on two long-acting injectable medications to help maintain adherence. We were able to eliminate his active psychotic symptoms and return him to normal functioning in affect and thinking, achieving sustained compliance with treatment. We identified multiple inconsistencies in screening for cancer of all types in these patients, masking of signs and symptoms that would typically clue physicians to the presence of cancers, underreporting of symptoms, and disparate access to healthcare resources in patients with mental disorders when compared to the general population. Treatment of cancer in these patients as compared to the general population has also been shown to be incongruent, which will be elaborated upon. Psychiatric interventions, as well as supportive measures, for treating patients who are facing challenges during active cancer treatment will be discussed.
    Challenges in Treating Cancer Patients With Unstable Psychiatric Disorder.
    World journal of oncology, Oct 2021 [PubMed 34804276]
  • Due to lack of pediatric-specific data, the management of chronic myeloid leukemia (CML) in pediatric, adolescents, and young adults is guided by adult CML evidence-based recommendations. Pediatric CML presents differently than adult CML and is often a more aggressive disease with different biological and host factors, yet there is sparse literature on how to address those differences. Over the past two decades, tyrosine kinase inhibitors (TKIs) have changed the way CML is treated. There are currently three FDA-approved TKIs (imatinib, dasatinib, and nilotinib) for pediatric patients. When choosing which TKI to begin treatment with, there are many factors that should be considered on a case-to-case basis to obtain optimal outcomes. The safety profiles for long-term TKI use in pediatrics require further study. Unlike adults, children are still actively growing during TKI use, and the effect on development can be detrimental. TKI therapy is not recommended during pregnancy with variable but significant risk of fetal abnormalities and miscarriage, warranting counseling for young female patients prior to beginning TKIs. Attempts for treatment-free remission (TFR) by planned TKI cessation in eligible adult patients in deep and sustained molecular remission are now done as a standard of practice. However, data is sparse in the pediatric population. There is currently an ongoing Children's Oncology Group (COG) study to determine the feasibility of TFR as a treatment goal. Further research and additional pediatric trials are needed to characterize the unique aspects of CML in children and adolescents and optimize outcomes.
    Management of Chronic Myeloid Leukemia in Children and Young Adults.
    Current hematologic malignancy reports, Oct 2022 [PubMed 35920965]


scroll to top