Coexistence of aberrant hematopoietic and stromal elements in myelodysplastic syndromes

Abbas, Salar ; Kini, Archana ; Srivastava, Vivi M. ; M, Marie Therese ; Nair, Sukesh C. ; Abraham, Aby ; Mathews, Vikram ; George, Biju ; Kumar, Sanjay ; Venkatraman, Aparna ; Srivastava, Alok (2017) Coexistence of aberrant hematopoietic and stromal elements in myelodysplastic syndromes Blood Cells, Molecules, and Diseases, 66 . pp. 37-46. ISSN 1079-9796

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Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. Several studies have shown the role of the bone marrow microenvironment in regulating hematopoietic stem, and progenitor function and their individual abnormalities have been associated with disease pathogenesis. In this study, we simultaneously evaluated hematopoietic stem cells (HSC), hematopoietic stem progenitor cells (HSPCs) and different stromal elements in a cohort of patients with MDS-refractory cytopenia with multilineage dysplasia (RCMD). Karyotyping of these patients revealed variable chromosomal abnormalities in 73.33% of patients. Long-term HSC and lineage-negative CD34 + CD38 − cells were reduced while among the HPCs, there was an expansion of common myeloid progenitor and loss of granulocyte-monocyte progenitors. Interestingly, loss of HSCs was accompanied by aberrant frequencies of endothelial (ECs) (CD31 + CD45 − CD71 −) and mesenchymal stem cells (MSCs) (CD31 − CD45 − 71 −) and its subsets associated with HSC niche. We further demonstrate down-regulation of HSC maintenance genes such as Cxcl12, VEGF in mesenchymal cells and a parallel upregulation in endothelial cells. Altogether we report for the first time quantitative and qualitative de novo changes in hematopoietic stem and its associated niche in a cohort of MDS-RCMD patients. These findings further reinforce the role of different components of the bone marrow microenvironment in MDS pathogenesis and emphasize the need for comprehensive simultaneous evaluation of all niche elements in such studies.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:MDS; Myelodysplastic Syndrome; Stem Cell Niche; Hematopoietic Cells; Stromal Cells
ID Code:114071
Deposited On:07 Jun 2018 11:18
Last Modified:07 Jun 2018 12:13

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