SF3B1 deficiency impairs human erythropoiesis via activation of p53 pathway: implications for understanding of ineffective erythropoiesis in MDS

SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), cha...
Source: Journal of Hematology and Oncology - Category: Hematology Authors: Tags: Research Source Type: research

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This article provides a brief, but comprehensive, review of our current understanding of clonal evolution in AA and concludes with 3 cases that illustrate a practical approach for integrating results of next-generation molecular studies into the clinical care of AA patients in 2018. PMID: 30504346 [PubMed - in process]
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
BCOR, encoding BCL-6 corepressor (BCOR), is X-linked and targeted by somatic mutations in various hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice lacking Bcor exon 4 (BcorE4/y) in the hematopoietic compartment developed NOTCH-dependent acute T-cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9 and 10 (BcorE9-10/y), which express a carboxyl-terminal truncated BCOR that fails to interact with core effector components of polycomb repressive complex 1.1. BcorE9-10/y mice developed lethal T-ALL in a similar manner to BcorE4/y mice, whereas BcorE...
Source: Blood - Category: Hematology Authors: Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research
Myelodysplastic syndrome (MDS) is a heterogeneous group of disorders characterized by clonal, dysplastic, ineffective hematopoiesis and an increased propensity to develop acute myeloid leukemia (AML) [1]. Approximately 60% to 80% of patients with MDS experience symptomatic anemia, and 40% to 50% may develop transfusion-dependent anemia. Transfusion-dependent anemia is associated with the development of iron overload and decreased survival. However, iron overload may occur before patients become transfusion-dependent, since ineffective erythropoiesis suppress hepcidin production in the liver and may lead to increased iron a...
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Anemia is the defining cytopenia of MDS patients, yet the molecular mechanisms for dyserythropoiesis in MDSs remain to be fully defined. Recent studies have revealed that heterozygous loss-of-function mutation of DNA dioxygenase TET2 is 1 of the most common mutations in MDSs and that TET2 deficiency disturbs erythroid differentiation. However, mechanistic insights into the role of TET2 on disordered erythropoiesis are not fully defined. Here, we show that TET2 deficiency leads initially to stem cell fac...
Source: Blood - Category: Hematology Authors: Tags: Red Cells, Iron, and Erythropoiesis Source Type: research
Conclusions: Testing for pnh was infrequent in mds patients, and the criteria for testing were heterogeneous. Clinical indicators prompted pnh testing in 6 of 11 patients. Given that effective treatment is now available for pnh and that patients with pnh-positive mds can respond to immunosuppressive therapy, pnh testing in mds should be considered. Prospective analyses to clarify the clinical significance of pnh positivity in mds are warranted. PMID: 30464689 [PubMed - in process]
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
The transforming growth factor beta (TGF-β) signaling pathway controls hematopoietic stem cell (HSC) behavior in the marrow niche; however, TGF-β signaling becomes chronic in early-stage myelodysplastic syndrome (MDS). Although TGF-β signaling normally induces negative feedback, in early-stage MDS, high levels of microRNA-21 (miR-21) contribute to chronic TGF-β signaling. We found that a TGF-β signal–correlated gene signature is sufficient to identify an MDS patient population with abnormal RNA splicing (eg, CSF3R) independent of splicing factor mutations and coincident with low HNRNPK activi...
Source: Blood - Category: Hematology Authors: Tags: Myeloid Neoplasia, e-Blood Source Type: research
Authors: Yamauchi R, Takata K, Shinagawa Y, Tanaka T, Fukuda H, Fukuda S, Kunimoto H, Umeda K, Morihara D, Yokoyama K, Takeyama Y, Irie M, Shakado S, Mizoguchi M, Hisano S, Yoshimitsu K, Sakisaka S Abstract A 70-year-old man was admitted for treatment of a single liver nodule that was detected by contrast-enhanced computed tomography. Twenty years earlier, the patient had been diagnosed with myelodysplastic syndrome-refractory anemia and secondary hemochromatosis but had not received erythrocyte transfusions. The current histological, computed tomography, and magnetic resonance imaging findings revealed hepatocellu...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Recurring chromosome abnormalities are frequent events in cancer and are especially prevalent in hematologic neoplasms. Somatic heterozygous deletions on chromosome 20q are detected in a variety of hematopoietic malignancies including myelodysplastic syndrome (MDS), classical myeloproliferative neoplasm (MPN), MDS/MPN overlap disorders such as chronic myelomonocytic leukemia (CMML), and acute leukemias. Del(20q) is especially prevalent in MPN patients (~10-15%), where it is the most commonly detected cytogenetic abnormality associated with primary myelofibrosis (PMF) and post-polycythemia vera myelofibrosis (MF). This sugg...
Source: Blood - Category: Hematology Authors: Tags: 635. Myeloproliferative Syndromes: Basic Science: Mechanisms of Development and Progression Source Type: research
We describe conditional survival and cause-specific mortality (disease-related [DRM], non-disease-related [NDRM], and GvHD-related) after alloHCT to provide clinically relevant information for patients who have survived 6 mos, 1, 2, 5, and 10y after alloHCT. Methods: From 1976 to 2013, 4,315 consecutive patients underwent alloHCT for hematologic diseases at a single institution. Vital status and cause of death were determined using the National Death Index Plus and medical records. Results: Diagnoses included acute leukemia (54%), chronic leukemia (17%), lymphoma (11%), myelodysplastic syndrome (10%), severe aplastic anemi...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Myeloid Malignancies and Allogeneic Stem Cell Transplant Source Type: research
We report the results of a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of luspatercept in patients with anemia due to Revised International Prognostic Scoring System (IPSS-R)-defined Very low-, Low-, or Intermediate-risk MDS with RS who require RBC transfusions. ClinicalTrials.gov identifier: NCT02631070.Methods: Eligible patients were aged ≥ 18 years; had IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with RS according to the WHO 2016 criteria; were refractory, intolerant, or ineligible to receive erythropoiesis-stimulating agents (ESAs); and required RBC tr...
Source: Blood - Category: Hematology Authors: Tags: Plenary Scientific Session Source Type: research
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