Aplastic anemia and clonal evolution: germ line and somatic genetics.

Aplastic anemia and clonal evolution: germ line and somatic genetics. Hematology Am Soc Hematol Educ Program. 2016 Dec 02;2016(1):74-82 Authors: Shimamura A Abstract Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF. Most germ line genetic BMF disorders are characterized by a high propensity to develop MDS or AML. Many affected patients lack the physical stigmata traditionally associated with the inherited marrow failure syndromes. Although any single inherited marrow failure disorder is rare, multiplexed genetic sequencing that allows simultaneous evaluation of marrow failure genes en masse demonstrated that, as a group, these inherited disorders compose a significant subset (5% to 10%) of patients with BMF. Early diagnosis of a germ line genetic marrow failure disorder allows individualized monitoring and tailored therapy. Recent studies of somatic variants in marrow failure revealed a high frequency of clonal hematopoiesis wit...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

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This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy.MethodsAll patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus.ResultsDuring the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the...
Source: Journal of Microbiology, Immunology and Infection - Category: Microbiology Source Type: research
Acquired aplastic anemia and inherited bone marrow failure syndromes both present with pancytopenia and must be distinguished because they have differences in treatment decisions and continued monitoring requirements. Advances in the genetic interrogation of patient samples have led to identification of inherited germline diseases and appreciation that patients with inherited bone marrow failure disorders may be normal in appearance with few expected clinical clues. Somatic mutations in aplastic anemia may have prognostic value. Hematopoietic stem cells from inherited marrow failure diseases can correct the proliferative d...
Source: Hematology/Oncology Clinics of North America - Category: Cancer & Oncology Authors: Source Type: research
Conclusion: Complex karyotype was most frequently associated with myelodysplastic syndromes and acute myeloid leukemia. Trisomy 21 and deletion 5q were the commonest cytogenetic abnormalities found. We also assessed complex karyotype in benign diseases and detected one patient of aplastic anemia with complex karyotype. This is the first study highlighting the presence of complex karyotypes in hematological disorders in our region. PMID: 29971104 [PubMed]
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy.MethodsAll patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus.ResultsDuring the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the...
Source: Journal of Microbiology, Immunology and Infection - Category: Microbiology Source Type: research
Pediatric myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal disorders with an annual incidence of 1 to 4 cases per million, accounting for less than 5% of childhood hematologic malignancies. MDSs in children often occur in the context of inherited bone marrow failure syndromes, which represent a peculiarity of myelodysplasia diagnosed in pediatric patients. Moreover, germ line syndromes predisposing individuals to develop MDS or acute myeloid leukemia have recently been identified, such as those caused by mutations in GATA2, ETV6, SRP72, and SAMD9/SAMD9-L. Refractory cytopenia of childhood (RCC) is the m...
Source: Blood - Category: Hematology Authors: Tags: Pediatric Hematology, Transplantation, How I Treat, Free Research Articles, Myeloid Neoplasia Source Type: research
Acquired aplastic anemia (AA) represents bone marrow (BM) failure caused by immune-system-mediated destruction of hematopoietic stem cells (HSCs) [1]. Gene expression profiling of AA HSCs suggests the presence of a stressed and immunologically activated target cell population [2]. Next-generation sequencing studies have identified somatic mutations, particularly in BCOR/BCORL1, PIGA, DNMT3A, and ASXL1, in AA patients [3,4]. Clonal hematopoiesis (CH) in AA is associated with evolution to myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) [1].
Source: Experimental Hematology - Category: Hematology Authors: Tags: Brief Communication Source Type: research
Conclusion Patients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.
Source: Journal of Microbiology, Immunology and Infection - Category: Microbiology Source Type: research
Authors: West AH, Churpek JE Abstract Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other physical features that are often recognizable early in life. However, increasing application of genomic sequencing and clinical awareness of subtle disease presentations have led to the recognition of IBMFS in pediatric and adult populations more frequently than previously realized, such as those with early onset myelodysplastic syndrome (MDS). Given the well-defined differences in clinical management needs and outc...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Conclusion This study tentatively suggests that the diagnosis of childhood malignancy follows a seasonal trend in Korea, and has a possible correlation with viral prevalence in several diseases. Further long-term analysis of epidemiological data is needed to explore possible causality.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Conclusions Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns. Patient summary Updated Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial findings show that radium-223 remained well tolerated during treatment and up to 3 yr after each patient's first injection. Three-year safety follow-up of Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial patients with castration-resistant prostate cancer and symptomatic bone metastases revealed a continued low incidence of myelosuppression, minimal nonhematologic adverse...
Source: European Urology - Category: Urology & Nephrology Source Type: research
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