Development of Cytogenetic Abnormalities in Myelodysplastic Syndromes

Bandara Wmms,Rathnayake Ajis

doi:10.4172/1747-0862.1000217

Bandara Wmms, Rathnayake Ajis

Open Access

https://doi.org/10.4172/1747-0862.1000217

Copy DOI

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis resulting in cellular dysplasia and peripheral cytopenias. Research into MDS have found that both hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) in the nurturing niche of HSCs are genetically altered in MDS. In this review we present the existing views on the origin of cytogenetic abnormalities in HSC and MSC compartments in MDS. Based on the available data, we speculate that the origin of the chromosomal aberrations of the hematopoietic compartment occurs at the hematopoietic stem/ progenitor level. The genetic aberrations in MSC compartment appears to initiate independently from their hematopoietic counterparts. Whether the genetic events in both HSC and MSC compartments which lead to MDS occur simultaneously or at different time points in the disease development need to be determined in future.

Highlights

Myelodysplastic Syndromes (MDS) result from malignant transformation of a hematopoietic stem cells (HSCs), which has growth advantage over normal HSCs resulting in an abnormal clone of cells [1,2]
Research has found that mesenchymal stem cells (MSCs), which give rise to most of the stromal components of the marrow is altered in MDS [4,5]
Whether the genetic events in both HSC and MSC compartments that lead to MDS occur simultaneously or at different time points in the disease development pathway has no clear answer

Summary

Introduction

Myelodysplastic Syndromes (MDS) result from malignant transformation of a HSC, which has growth advantage over normal HSCs resulting in an abnormal clone of cells [1,2]. The genetic abnormalities present in MDS are thought to initiate at the level of stem cells in the hematopoietic and mesenchymal compartments [5,6]. These genetic abnormalities occur due to previous exposure to mutagens like benzene, alkylating agents, gasoline, topoisomerase II inhibitors, radiation etc. MDS blasts become less apoptotic with increased proliferative capacity, producing phenotypically immature clone of cells, whereas the T-cell compartment shows decreased proliferation and increased apoptosis [27,28,29,30,31,32]. Complex interactions between the abnormal clones of HSCs and the neighboring cells of the marrow microenvironment may modulate the disease development

The occurrence of cytogenetic abnormalities in MDSHSCs

Findings

Conclusion