Leukemia research
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B-cell maturation antigen (BCMA), a tumor necrosis factor receptor (TNFR) family member, is selectively expressed on terminally differentiated B-lymphocytes including multiple myeloma (MM) tumor cells. We sought to determine whether circulating (c)BCMA in MM serum interferes with antiBCMA antibody binding to MM cells. An enzyme-linked immunosorbent assay (ELISA) was used to determine serum (s) BCMA levels among 379 samples from patients with relapsed/refractory MM (RRMM). ⋯ We have shown that BCMA is elevated in the serum from MM patients and that the median concentration of sBCMA from RRMM patients was 176 ng/mL (n = 379). Additionally, there was a consistent decrease in the binding of anti-BCMA antibody to MM tumor cells with sBCMA level ≥156 ng/mL. Together, these results demonstrate that circulating BCMA levels in most RRMM patients are high enough to interfere with anti-BCMA antibody binding to MM tumor cells and may interfere with BCMA-targeted immune-based therapies.
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Incorporation of ABL-targeted oral tyrosine kinase inhibitors (TKIs) into frontline therapeutic regimens has improved outcomes for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, patients with persistent minimal residual disease (MRD) exhibit increased risk of relapse. Combining consolidative chemotherapy with TKIs may increase rates of infectious complications, organ toxicity, hospitalization, and non-relapse mortality. ⋯ Cytokine release syndrome (all grade 1-2) was observed in 3/11 patients; one patient experienced transient grade 1 neurologic toxicity. Transient grade 2 transaminitis was observed in 6/11 patients, including 4/5 recipients of blinatumomab + ponatinib. This small series suggests blinatumomab + TKI is a safe and effective consolidation strategy for patients with Ph + ALL to achieve or maintain CMR.
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Germline mutation in GATA2 can lead to GATA2 deficiency characterized by a complex multi-system disorder that can present with many manifestations including variable cytopenias, bone marrow failure, myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), and severe immunodeficiency. Penetrance and expressivity within families is often variable. There is a spectrum of bone marrow disease in symptomatic cytopenic patients ranging from hypocellular marrows without overt dysplasia to those with definitive MDS, AML, or chronic myelomonocytic leukemia. ⋯ MDS-associated mutations were identified in symptomatic GATA2 patients both with overt MDS and in those with hypocellular/aplastic bone marrows without definitive dysplasia. Healthy relatives of probands harboring the same germline GATA2 mutations had essentially normal marrows that were overall devoid of MDS-associated mutations. The findings suggest that abnormal clonal hematopoiesis is a common event in symptomatic germline mutated GATA2 patients with MDS and also in those with hypocellular marrows without overt morphologic evidence of dysplasia, possibly indicating a pre-MDS stage warranting close monitoring for disease progression.
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Acute myeloid leukemia (AML) is a heterogeneous disease. Until recently, treatment for patients with AML was limited to induction chemotherapy with cytarabine and anthracycline or hypomethylating agents, and, in some instances, allogeneic hematopoietic stem cell transplant. With the recent approval of new therapies-i.e., CPX-351, enasidenib, ivosidenib, gemtuzumab ozogamicin, and midostaurin-a new era in AML treatment has emerged. ⋯ This review discusses data, including associated safety profiles that supported these recent approvals, and provides insights to help clinicians navigate new therapy options for this devastating disease. Given the heterogeneity of AML, the treatment landscape will likely continue to grow and evolve as additional agents (and their combinations) are approved for the treatment of subpopulations of patients with AML. Physicians will need to remain abreast of the ever-changing treatment landscape.
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The development of circular RNA (circRNA) microarrays has facilitated studies on the role of circRNAs in regulating gene expression through a circRNA-miRNA-mRNA network. In our study, a microarray was used to detect the expression profiles of circRNAs in mouse bone marrow stromal cell (MSCs) after total body irradiation (TBI) in an X-ray field. Forty mice were randomly distributed into two groups, the control group and the TBI group, with 20 mice in each. ⋯ The miRNA support vector regression method was used to predict potential target miRNAs for the circRNAs while ClueGO was used for functional analysis of predicted miRNA target genes. This is the first study to investigate the differential circRNA expression profile in TBI and the associated functions. Significantly upregulated or downregulated circRNAs may represent novel biomarkers and novel therapeutic targets for the clinical management of radiation injury with TBI.