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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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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
Conclusion SDF-1/CXCR4 axis plays a crucial role in engraftment; however, more studies are warranted to assess their expression post-transplant. Evaluating the ligand (chemokine, SDF-1) or its receptor (CXCR4) may serve as potential surrogate markers for assessment of engraftment.
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
Myeloid malignancies can be either primary or secondary, whether or not a specific cause can be determined. Fanconi anemia (FA), a rare constitutional bone marrow failure, usually presents an increased possibility of clonal evolution, due to the increase in chromosomal instability, TP53 activation, and cell death. The evolution of FA may include aplastic anemia by the progressive failure of the bone marrow and myelod neoplasias, such as acute myeloid leukemia and myelodysplastic syndrome. Chromosome abnormalities, particularly of chromosomes, 1, 3, and 7, during the aplastic phase of the disease are predictive of evolution...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research
Clonal hematopoiesis (CH) in aplastic anemia (AA) has been closely linked to the evolution of late clonal disorders, including paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), which are common complications after successful immunosuppressive therapy (IST). With the advent of high-throughput sequencing of recent years, the molecular aspect of CH in AA has been clarified by comprehensive detection of somatic mutations that drive clonal evolution. Genetic abnormalities are found in ~50% of patients with AA and, except for PIGA mutations and copy-neutral loss-of-heterozygosi...
Source: Blood - Category: Hematology Authors: Tags: Free Research Articles, Red Cells, Iron, and Erythropoiesis, CME article, Review Articles Source Type: research
Publication date: September–December 2014 Source:Best Practice & Research Clinical Haematology, Volume 27, Issues 3–4 Author(s): Blanche P. Alter Fanconi anemia (FA) is a rare autosomal recessive cancer-prone inherited bone marrow failure syndrome, due to mutations in 16 genes, whose protein products collaborate in a DNA repair pathway. The major complications are aplastic anemia, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and specific solid tumors. A severe subset, due to mutations in FANCD1/BRCA2, has a cumulative incidence of cancer of 97% by age 7 years; the cancers are AML, brain ...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
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