Unveiling the paradoxical nature of myelodysplastic syndromes (MDS): Why hypercellular marrow strongly favors accelerated apoptosis. | Aplastic Anemia & MDS International Foundation Return to top.

Unveiling the paradoxical nature of myelodysplastic syndromes (MDS): Why hypercellular marrow strongly favors accelerated apoptosis.

Journal Title: 
Biochem Cell Biol
Primary Author: 
Das M
Author(s): 
Das M, Chaudhuri S, Law S.
Original Publication Date: 
Thursday, March 21, 2013

The pathogenesis of bone marrow failure in myelodysplastic syndromes (MDS) is an unresolved mystery. MDS causes peripheral blood cytopenias and increased bone marrow cellularity. This apparent paradox has been interpreted as a sign of intramedullary destruction of a substantial portion of the developing hematopoietic cells by apoptosis. The present study aimed to delineate the exact mechanistic relationship between the bone marrow hypercellularity and the accelerated apoptosis in an N-ethyl-N-nitrosourea (ENU)-induced experimental MDS mouse model. The observations made so far clarify the quantitative and qualitative changes that occur in the bone marrow microenvironment through cell cycle analysis, especially involving the telomerase reverse transcriptase (TERT) and p53 expression patterns. The survival fate of the bone marrow cells were observed by measuring the expression level of some intracellular protein molecules like apoptosis signal-regulating kinase 1 (ASK-1), c-Jun N-terminal kinase (JNK), and cleaved caspase-3 of the extrinsic pathway toward apoptosis. We found myelodysplasia damage occurs within one or more multipotent progenitor populations resulting in uncontrolled cellular proliferation within the MDS bone marrow. Then, due to homeostatic balance, this high cellular burden is minimized by activating the apoptosis pathway. As a result, the peripheral blood suffers cellular deprivation. This study can throw some light on the mechanism of disease progression and also help to reveal the paradoxical nature of the disease.

Bone Marrow Disease(s): 
  • myelodysplastic syndromes (MDS)
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