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IDH1 Mutation Is an Independent Inferior Prognostic Indicator for Patients with Myelodysplastic Syndromes

Background: Genomic sequencing technologies have identified isocitrate dehydrogenase (IDH) mutations in haematological malignancies. The prognostic implications of somaticIDH mutation (mIDH) in myelodysplastic syndromes (MDS) remain controversial.Methods: Mutations inIDH1 andIDH2were detected using genomic sequencing technologies in 97 patients with MDS.Results: Seven (7.2%) mutations were identified: 3 inIDH1 (all R132C) and 4 inIDH2 (3 R140Q and 1 R140L). The frequency of mutation was 16.6% (2/12) in refractory anaemia with excess blasts (RAEB)-1 and 14.7% (5/34) in RAEB-2.IDH1/2 mutations were closely associated with higher bone marrow blast counts (median 10.0 vs. 2.3%;p = 0.019) and lower absolute neutrophil counts (median 0.44 × 109/L vs. 1.21 × 109/L; p = 0.027). AllIDH mutations were mutually exclusive and heterozygous.IDH mutations were not significantly correlated with any specific karyotype. Patients withIDH1 mutations exhibited shorter overall and progression-free survival (OS and PFS;p = 0.039 andp = 0.042, respectively), whereasIDH2 mutations did not affect OS or PFS (p = 0.560 andp = 0.218, respectively). Multivariate analysis indicated thatIDH1 mutation (p = 0.018; hazard ratio [HR] 4.735; 95% confidence interval [CI] 1.299-17.264), karyotype risk (p = 0.036; HR 1.619; 95% CI 1.033-2.539) and the revised International Prognostic Scoring System risk category (p
Source: Acta Haematologica - Category: Hematology Source Type: research

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Authors: Vlachos A Abstract A mutation in the gene encoding the small subunit-associated ribosomal protein RPS19, leading to RPS19 haploinsufficiency, is one of the ribosomal protein gene defects responsible for the rare inherited bone marrow failure syndrome Diamond Blackfan anemia (DBA). Additional inherited and acquired defects in ribosomal proteins (RPs) continue to be identified and are the basis for a new class of diseases called the ribosomopathies. Acquired RPS14 haploinsufficiency has been found to be causative of the bone marrow failure found in 5q- myelodysplastic syndromes. Both under- and overexpressio...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Alter BP Abstract Patients with inherited bone marrow failure syndromes are usually identified when they develop hematologic complications such as severe bone marrow failure, myelodysplastic syndrome, or acute myeloid leukemia. They often have specific birth defects or other physical abnormalities that suggest a syndrome, and sequencing of specific genes or next-generation sequencing can determine or confirm the particular syndrome. The 4 most frequent syndromes are Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond syndrome. This review discusses the major complications...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program 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
Authors: Maciejewski JP, Balasubramanian SK Abstract Recent technological advances in genomics have led to the discovery of new somatic mutations and have brought deeper insights into clonal diversity. This discovery has changed not only the understanding of disease mechanisms but also the diagnostics and clinical management of bone marrow failure. The clinical applications of genomics include enhancement of current prognostic schemas, prediction of sensitivity or refractoriness to treatments, and conceptualization and selective application of targeted therapies. However, beyond these traditional clinical aspects, ...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Abstract Disease overviewThe myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DiagnosisDiagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis. Ri...
Source: American Journal of Hematology - Category: Hematology Authors: Tags: ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES Source Type: research
We present a 2-year-old boy with splenomegaly, leukocytosis, thrombocytopenia, anemia, and excess myeloblasts with easily seen Auer rods, and marked dysgranulopoiesis and dyserythropoiesis. Conventional cytogenetic analysis showed a sole abnormality of t(3;5)(q25;q35). Microarray analysis showed a terminal 21 Mb region of copy-neutral loss of heterozygosity on 19q. Disease-related somatic NRAS mutation was detected. This case represents an unusual JMML with Auer rods and marked myelodysplasia. These unusual histopathologic features may be related to the t(3;5)(q25;q35). A t(3;5) with variable breakpoints has been reported ...
Source: Pathology Research and Practice - Category: Pathology Source Type: research
Conclusion: DAH is a severe disorder, with nonspecific presentation, caused by a wide spectrum of disease, as demonstrated by this series. Diagnosis requires high clinical suspicion and a thorough work-up.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Diffuse Parenchymal Lung Disease Source Type: research
Conditions:   Acute Myeloid Leukemia;   Blasts 30 Percent or Less of Bone Marrow Nucleated Cells;   Chronic Myelomonocytic Leukemia;   High Risk Myelodysplastic Syndrome;   Myelodysplastic Syndrome;   Refractory Anemia Interventions:   Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401;   Drug: Decitabine;   Other: Laboratory Biomarker Analysis;   Biological: Nivolumab;   Drug: Poly ICLC Sponsors:   Roswell Park Cancer Institute;   National Cancer Instit...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
More News: Anemia | Cancer & Oncology | Hematology | Myelodysplastic Syndrome