Nonclonal neutrophil responses after successful treatment of myelodysplasia with low-dose 5-aza-2’-deoxycytidine (decitabine)

Effects of 5-aza-2′-deoxycytidine on proliferation, differentiation and p15/INK4b regulation of human hematopoietic progenitor cells

“…This model therefore appears suitable also for global analyses of gene methylation and expression profiling during lineagespecific maturation. Finally, that this demethylating agent, particularly in combination with an HDAC inhibitor, is able to expand primitive hematopoietic progenitors 17 may also partly explain the in vivo emergence of normal hematopoiesis 32,35 in MDS and AML patients treated with low doses of DAC.…”

Clonality of the stem cell compartment during evolution of myelodysplastic syndromes and other bone marrow failure syndromes

“…40,41 Treatment with 5-azacytidine resulted in the elimination of the abnormal clone from the granulocytic population as measured by interphase FISH. 42 It is possible that, unlike in AML where all mature cells can only reflect residual normal hematopoiesis, in MDS the aberrant clone is capable of the production/function of mature progeny so that differentiated progeny may correspond to a mixture of both clonal and normal cells. 39,40,43 However, the ability to produce differentiated progeny may depend on the type of the genetic lesion that in certain circumstances may result in a total maturation block.…”

Optimizing hypomethylating agents in myelodysplastic syndromes

“…In addition, the recent discovery of mutations in the splicing machinery in MDS [6] may lead to re-evaluation of the biological consequences of translational repression caused by RNA incorporation of AZA (but not of DAC) [7 & ]. Newly established in-vivo models [8] will help understand the cellular fate after HMA exposure, which could involve the DNA damage response pathway [9,10], autophagy [11], and possibly differentiation of dysplastic cells [12,13].…”