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Somatic mutations and clonal hematopoiesis in congenital neutropenia

Severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome (SDS) are congenital neutropenia syndromes with a high rate of leukemic transformation. Hematopoietic stressors may contribute to leukemic transformation by increasing the mutation rate in hematopoietic stem/progenitor cells (HSPCs) and/or by promoting clonal hematopoiesis. We sequenced the exome of individual hematopoietic colonies derived from 13 patients with congenital neutropenia to measure total mutation burden and performed error-corrected sequencing on a panel of 46 genes on 80 patients with congenital neutropenia to assess for clonal hematopoiesis. An average of 3.6 ± 1.2 somatic mutations per exome was identified in HSPCs from patients with SCN compared with 3.9 ± 0.4 for healthy controls (P = NS). Clonal hematopoiesis due to mutations in TP53 was present in 48% (13/27) of patients with SDS but was not seen in healthy controls (0/17, P
Source: Blood - Category: Hematology Authors: Tags: Hematopoiesis and Stem Cells, Pediatric Hematology, Phagocytes, Granulocytes, and Myelopoiesis Source Type: research

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Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
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Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
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Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Authors: Cabezón M, Bargay J, Xicoy B, García O, Borrás J, Tormo M, Marcé S, Pedro C, Valcárcel D, Jiménez MJ, Guàrdia R, Palomo L, Brunet S, Vall-Llovera F, Garcia A, Feliu E, Zamora L, CETLAM Group Abstract Myelodysplastic syndromes (MDS) are stem cell disorders caused by various gene abnormalities. We performed targeted deep sequencing in 39 patients with high-risk MDS and secondary acute myeloid leukemia (sAML) at diagnosis and follow-up (response and/or relapse), with the aim to define their mutational status, to establish if specific mutations are biomarkers of...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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Source: Hematology Oncology Clinics of North America - Category: Hematology Source Type: research
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Source: Annals of Hematology - Category: Hematology Source Type: research
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Source: Mayo Clinic Proceedings - Category: Internal Medicine Authors: Tags: Residents' Clinic Source Type: research
We report a case of myeloid sarcoma with megakaryoblastic differentiation in the breast of a patient with history of essential thrombocythemia. The mass was composed of undifferentiated pleomorphic malignant cells in trabecular cords and nests with many scattered giant malignant cells and brisk abnormal mitoses. On immunohistochemistry, the neoplastic cells were positive for CD61, CD31, CD34, Factor VIII and CD43 which confirmed the diagnosis. To our knowledge, this is the first report of myeloid sarcoma with megakaryoblastic morphology occurring in the breast. Here we discuss the clinicopathologic features of this rare en...
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
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Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research
Contributors : Aniththa Thivakaran ; Lacra Botezatu ; Judith H önes ; Judith Schütte ; Lothar Vassen ; Nadine Olberding ; Yahya S Al-Matary ; Renata Köster ; Klaus Lennartz ; Andre Görgens ; Bernd Giebel ; Bertram Opalka ; Ulrich Dührsen ; Cyrus KhandanpourSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusDifferentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukem...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
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