Hits 1 - 10 (out of 7001 matching entities) [14601 mentions] (46 ms):
1. chronic myeloid leukemias

11822 articles, score 3864.530

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Abstracts

  • Treatment of chronic myeloid leukemia has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs), and treatment guidelines based on numerous clinical trials are available for chronic phase disease. However for CML in the blast phase (CML-BP), prognosis remains poor and treatment options are much more limited. The spectrum of treatment strategies for children and adolescents with CML-BP has largely evolved empirically and includes treatment principles derived from adult CML-BP and pediatric acute leukemia. Given this heterogeneity of treatment approaches, we formed an international panel of pediatric CML experts to develop recommendations for consistent therapy in children and adolescents with this high-risk disease based on the current literature and national standards. Recommendations include detailed information on initial diagnosis and treatment monitoring, differentiation from Philadelphia-positive acute leukemia, subtype-specific selection of induction therapy, and combination with tyrosine kinase inhibitors. Given that allogeneic hematopoietic stem cell transplantation currently remains the primary curative intervention for CML-BP, we also provide recommendations for the timing of transplantation, donor and graft selection, selection of a conditioning regimen and prophylaxis for graft-versus-host disease, post-transplant TKI therapy, and management of molecular relapse. Management according to the treatment recommendations presented here is intended to provide the basis for the design of future prospective clinical trials to improve outcomes for this challenging disease.
    Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations.
    Leukemia, Jan 2023 [PubMed 36707619]
  • 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]
  • 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

3461 articles, score 1030.252

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Enriched GO Terms

Abstracts

  • Patients with relapsed/refractory acute myeloid leukemia (r/r AML) are characterized as having a poor prognosis. The only viable option of treatment for these patients is allogenic stem cell transplantation (allo-HSCT). Therefore, we have attempted to analyse factors related to both the disease itself and the transplantation procedure that could have an influence on the improvement of outcomes in this group of patients. Sixty-four patients with r/r AML underwent allo-HSCT at our center in 2012 to 2021. Fifty-two had active disease at the beginning of theallo-HSCT procedure, with amedian number of blasts in bone marrow (BM) of 18, and 12 had therapeutic aplasia after the last reinduction (blasts < 5% in BM). The probability of overall survival (OS) at 2 years was 25%. The median follow-up for survivors was 21.5 months. Progression-free survival (PFS) estimates were above 46%. The main cause of death was disease progression (49%). A statistically significant effect on premature death was reported for the diagnosis of secondary AML (sAML) and cytomelovirus (CMV) reactivation post allo-HSCT. On the other hand, chronic graft versus host disease (cGVHD) decreased the risk of disease progression. sAML and CMV reactivation were found to have opposite effects.
    Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Acute Myeloid Leukemia: A Single-Centre Experience.
    Clinical lymphoma, myeloma & leukemia, Jan 2023 [PubMed 36323603]
  • 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, Aug 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]

3. leukemias

3212 articles, score 843.665

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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]
  • Disease progression and relapse of chronic myeloid leukemia (CML) are caused by therapy resistant leukemia stem cells (LSCs), and cure relies on their eradication. The microenvironment in the bone marrow (BM) is known to contribute to LSC maintenance and resistance. Although leukemic infiltration of the spleen is a hallmark of CML, it is unknown whether spleen cells form a niche that maintains LSCs. Here, we demonstrate that LSCs preferentially accumulate in the spleen and contribute to disease progression. Spleen LSCs were located in the red pulp close to red pulp macrophages (RPM) in CML patients and in a murine CML model. Pharmacologic and genetic depletion of RPM reduced LSCs and decreased their cell cycling activity in the spleen. Gene expression analysis revealed enriched stemness and decreased myeloid lineage differentiation in spleen leukemic stem and progenitor cells (LSPCs). These results demonstrate that splenic RPM form a niche that maintains CML LSCs in a quiescent state, resulting in disease progression and resistance to therapy.
    Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance.
    Leukemia, Nov 2022 [PubMed 36163264]
  • Suboptimal guideline adherence in chronic myeloid leukemia (CML) care is associated with worse treatment outcomes. Current study focused on adherence to seven quality indicators (QIs) based on the European Leukemia Network guideline (one diagnostic, one therapeutic, and five monitoring indicators). Data were obtained from population-based registries in the Netherlands of 405 newly diagnosed chronic phase CML patients between January 2008 and April 2013. Compliance rates regarding diagnostic and therapeutic indicator were 83% and 78%, respectively. Monitoring indicators rates were lower: 21-27% for indicators concerning the first year and 58% and 62% for the second and third year, respectively. Noncompliance occurred mostly due to non-timely monitoring. Twenty cases did not comply with any indicator, 6% complied with all indicators. After adjustment for age, overall survival rates did not differ significantly between the groups. Adherence to guideline-based QIs was suboptimal. This demonstrates the evidence-practice gap, shows room for improvement and underscores the need for real-world data.
    Adherence to quality indicators in chronic myeloid leukemia care: results from a population-based study in The Netherlands.
    Leukemia & lymphoma, Nov 2022 [PubMed 36369821]

4. imatinib

3875 articles, score 777.429

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Enriched GO Terms

Abstracts

  • The clinical presentation of chronic myeloid leukemia (CML) at diagnosis differs in children compared to adults. At younger age, anemia appears to be frequent at diagnosis, but its prevalence and its impact on prognosis are not well known. In the International Registry of Childhood CML, we selected children and adolescents in chronic phase at diagnosis of CML and treated upfront with imatinib. We examined their hemoglobin level at diagnosis according to the WHO grades to assess the prevalence of anemia and its impact on response to tyrosine kinase inhibitors (TKIs). Data on 430 patients were included. Anemia at diagnosis was observed in 350 patients (81%), with a mean hemoglobin level of 96.4 g/l (SD 23.6). Among them, 182 patients (52%) presented with moderate anemia and 110 (31%) with severe anemia while 58 (17%) had mild anemia. Compared with mild and no anemia, moderate and severe forms were significantly associated with younger age at diagnosis, asthenia, splenomegaly, and increased leukocyte and basophil counts. Delays in achieving major and deep molecular responses were significantly increased for patients with moderate and severe anemia, and also failure of imatinib treatment was more frequent in these two sub-cohorts. However, hemoglobin level was not significantly associated with survival. Anemia at diagnosis of pediatric CML was frequent and may be considered as a prognostic factor.
    Prevalence of anemia at diagnosis of pediatric chronic myeloid leukemia and prognostic impact on the disease course.
    Annals of hematology, Nov 2022 [PubMed 36370190]
  • 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]
  • Chronic myeloid leukemia (CML) is a clonal hematologic disorder characterized by t(9;22) translocation, in which cytogenetic aberrations can occur in Ph(+) and (-) clones. These aberrations develop due to clonal evolution as well as treatment and they have prognostic significance. They are grouped as major and minor route anomalies in terms of their effects on prognostic parameters, such as treatment response, overall survival (OS), disease stage, complete cytogenetic response (CCyR), and major molecular response (MMR). It is stated that major route anomalies have unfavorable prognostic effects compared to minor route anomalies. We aimed to investigate the frequency and prognostic effects of cytogenetic anomalies detected in Ph(+) and (-) clones. In this study, we retrospectively analyzed the cytogenetic results of 450 patients diagnosed with CML between 2005 and 2020. We detected cytogenetic aberrations in Ph-positive and negative clones in 41 of 450 patients. The most common anomalies were trisomy 8 (+8), additional Ph chromosome (+Ph), and loss of chromosome Y. Rarely, aneuploidy of the Y chromosome, dup (22), +11, and +6 were seen in CML patients. We observed that these identified aberrations negatively affected MMR and CCyR, and generally resulted in changing imatinib treatment for second-generation tyrosine kinase activity inhibitors. Our results are compatible with the literature. We suggest that cytogenetic aberrations detected in Ph(+) and (-) clones should be a warning sign in terms of treatment and require close observation. The use of cytogenetic methods for the identification of these anomalies is also important.
    The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)
    Turkish journal of haematology : official journal of Turkish Society of Haematology, Dec 2022 [PubMed 36199265]

5. lymphoblastic leukemia

1573 articles, score 364.895

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Abstracts

  • A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3-5 conditions. Logistic regression was used to estimate the risk of grade 3-4 conditions in BMT recipients who were alive at the time of this study compared with siblings. The median age at transplantation was 11.3 years (range, 0.4-22.0 years), and the median length of follow-up was 11.7 years (range, 2.0-45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3-4 condition was 53.8% (95% CI, 46.7%-60.3%). The adjusted odds ratio of a grade 3-4 condition was 15.1 in survivors (95% CI, 9.5-24.0) compared with siblings. The risk of a grade 3-5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01-1.05) and was higher among females (HR, 1.27; 95% CI, 1.02-1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27-2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09-1.74). Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3-4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.
    Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood.
    Cancer, Feb 2023 [PubMed 36484292]
  • Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for patients with high-risk acute leukemias, but unfortunately disease recurrence remains the major cause of death in these patients. Infusion of donor lymphocytes (DLI) has the potential to restore graft-versus-leukemia immunologic surveillance; however, efficacy varies across different hematologic entities. Although relapsed chronic myeloid leukemia, transplanted in chronic phase, has proven remarkably susceptible to DLI, response rates are more modest for relapsed acute myeloid leukemia and acute lymphoblastic leukemia. To prevent impending relapse, a number of groups have explored administering DLI preemptively on detection of measurable residual disease (MRD) or mixed chimerism. Evidence for the effectiveness of this strategy, although encouraging, comes from only a few, mostly single-center retrospective, nonrandomized studies. This article seeks to (1) discuss the available evidence supporting this approach while highlighting some of the inherent challenges of MRD-triggered treatment decisions post-transplant, (2) portray other forms of postremission cellular therapies, including the role of next-generation target-specific immunotherapies, and (3) provide a practical framework to support clinicians in their decision-making process when considering preemptive cellular therapy for this difficult-to-treat patient population.
    How I treat high-risk acute myeloid leukemia using preemptive adoptive cellular immunotherapy.
    Blood, Jan 2023 [PubMed 35512203]
  • 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]

6. BCR-ABL

2008 articles, score 359.697

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Not available

Enriched GO Terms

Not available

Abstracts

  • Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by a unique BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) were developed to target the BCR-ABL oncoprotein, inhibiting its abnormal kinase activity. TKI treatments have significantly improved CML patient outcomes. However, the patients can develop drug resistance and relapse after therapy discontinues largely due to intratumor heterogeneity. It is critical to understand the differences in therapeutic responses among subpopulations of cells. Single-cell RNA sequencing measures the transcriptome of individual cells, allowing us to differentiate and analyze individual cell populations. Here, we integrated a single-cell RNA sequencing profile of CML stem cells and network analysis to decipher the mechanisms of distinct TKI responses. Compared to normal hematopoietic stem cells, a set of genes that were concordantly differentially expressed in various types of stem cells of CML patients was revealed. Further transcription regulatory network analysis found that most of these genes were directly controlled by one or more transcript factors and the genes have more regulators in the cells of the patients who responded to the treatment. The molecular markers including a known drug-resistance gene and novel gene signatures for treatment response were also identified. Moreover, we combined protein-protein interaction network construction with a cancer drug database and uncovered the drugs that target the marker genes directly or indirectly via the protein interactions. The gene signatures and their interacted proteins identified by this work can be used for treatment response prediction and lead to new strategies for drug resistance monitoring and prevention. Our single-cell-based findings offered novel insights into the mechanisms underlying the therapeutic response of CML.
    Integrating Single-Cell Transcriptome and Network Analysis to Characterize the Therapeutic Response of Chronic Myeloid Leukemia.
    International journal of molecular sciences, Nov 2022 [PubMed 36430822]
  • /μl. Bone marrow pathology report findings were consistent with chronic myeloid leukemia (CML), and the BCR-ABL test came positive. CT chest with contrast showed a large chest wall lesion, suggestive of a Morel-Lavallee lesion. Ultrasound-guided aspiration of the lesion yielded 20 mm of fluid from the thick hematoma. Histopathology of the fluid showed Necrotic debris with mixed inflammation. Patient's condition improved, and he was discharged on Dasatinib with follow-up in hematology and surgery clinics.
    Chronic myelogenous leukemia presenting with Morel Lavallée lesion: A case report of a rare presentation.
    Clinical case reports, Dec 2022 [PubMed 36590661]
  • 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]

7. myelodysplastic syndromes

1248 articles, score 345.670

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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]
  • A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3-5 conditions. Logistic regression was used to estimate the risk of grade 3-4 conditions in BMT recipients who were alive at the time of this study compared with siblings. The median age at transplantation was 11.3 years (range, 0.4-22.0 years), and the median length of follow-up was 11.7 years (range, 2.0-45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3-4 condition was 53.8% (95% CI, 46.7%-60.3%). The adjusted odds ratio of a grade 3-4 condition was 15.1 in survivors (95% CI, 9.5-24.0) compared with siblings. The risk of a grade 3-5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01-1.05) and was higher among females (HR, 1.27; 95% CI, 1.02-1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27-2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09-1.74). Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3-4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.
    Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood.
    Cancer, Feb 2023 [PubMed 36484292]
  • 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]

8. BCR-ABL1

874 articles, score 318.048

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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

1100 articles, score 293.045

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Molecular Interaction Network

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Enriched GO Terms

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Abstracts

  • Large vessel vasculitis is characterized by chronic inflammation within the aortic wall and its major branches. The inflammation is considered to occur as a result of immune dysregulation. Hematologic malignancy is one of the rare causes of secondary vasculitis. Herein, we report a rare case of large vessel vasculitis associated with acute myeloid leukemia mimicking primary vasculitis.
    Large Vessel Vasculitis as an Initial Manifestation of Acute Myeloid Leukemia: A Case Report.
    Journal of the Korean Society of Radiology, Jul 2022 [PubMed 36238917]
  • Chronic myeloid leukemia (CML) is a malignant hematologic malignancy that can progress to blast phase with a myeloid or lymphoid phenotype. Some patients with CML can also progress to blast crisis phase; however, the transformation of CML into Philadelphia-positive lymphoma is extremely rare. fusion gene was undetectable in the peripheral blood. To our knowledge, this is the first patient known to have developed Philadelphia-positive ALCL transformed from CML. fusion.
    Sudden extramedullary and extranodal Philadelphia-positive anaplastic large-cell lymphoma transformation during imatinib treatment for CML: A case report.
    World journal of clinical cases, Oct 2022 [PubMed 36246839]
  • 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]

10. dasatinib

1088 articles, score 265.102

Entity Information

Molecular Interaction Network

Enriched GO Terms

Abstracts

  • /μl. Bone marrow pathology report findings were consistent with chronic myeloid leukemia (CML), and the BCR-ABL test came positive. CT chest with contrast showed a large chest wall lesion, suggestive of a Morel-Lavallee lesion. Ultrasound-guided aspiration of the lesion yielded 20 mm of fluid from the thick hematoma. Histopathology of the fluid showed Necrotic debris with mixed inflammation. Patient's condition improved, and he was discharged on Dasatinib with follow-up in hematology and surgery clinics.
    Chronic myelogenous leukemia presenting with Morel Lavallée lesion: A case report of a rare presentation.
    Clinical case reports, Dec 2022 [PubMed 36590661]
  • The management of chronic myeloid leukemia is associated with an extensive economic burden, and as novel interventions are being tested in this disease, understanding the comparative effectiveness is of interest. Findings and conclusions of this important issue continue to evolve with improvements in clinical research and economic understanding. This systematic literature review aims to conduct a comprehensive assessment of economic evaluations in chronic phase chronic myeloid leukemia. , and the National Health Service Economic Evaluation Database were searched on 4 July, 2022 to identify economic evaluations of chronic myeloid leukemia. Health technology assessment websites and key conference proceedings were also searched. Economic evaluations comparing treatment options in adult patients with chronic phase chronic myeloid leukemia were included. The quality of the studies were assessed using Drummond's checklists. The search retrieved 47 studies and 16 health technology assessments that fulfilled the eligibility criteria. Most were cost-utility analyses (23 studies and 11 health technology assessments) and were from the USA (n = 15) and China (n = 7). Twenty-seven studies and six health technology assessments included only patients with chronic phase chronic myeloid leukemia. Most models had a Markov structure, a 1 year to lifetime time horizon, and a 1-month cycle length. Commonly assessed treatments were various tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) and other interventions such as interferon-α, hydroxyurea, and allogeneic stem cell transplant. In patients with newly diagnosed chronic myeloid leukemia, imatinib regimens were cost effective, mostly owing to the availability of generics. Nilotinib and dasatinib were generally cost effective as second-line agents for patients who were resistant or intolerant to imatinib. Though progress has been made to better characterize the cost effectiveness of first-line and second-line chronic myeloid leukemia therapies, the paucity of published cost-effectiveness studies of third-line treatments increases the uncertainty associated with economic evaluations of later lines of therapy.
    A Systematic Literature Review of the Economic Evaluations of Treatments for Patients with Chronic Myeloid Leukemia.
    PharmacoEconomics, Dec 2022 [PubMed 36175789]
  • 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]


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