3.2 Aging . The Physiology Of Aging Hematopoiesis Represents

3.2 Aging The physiology of aging hematopoiesis represents an attractive research field given complex interaction between bone marrow microenvironment and hemopoietic stem cells. During aging, a gradual functional decline of various cellular subsets with different self-renewal and differentiation potential is dominant. However, it is recognized that shift toward preferential myeloid-biased hematopoiesis is a common event that anticipates disruption of normal molecular marrow homeostasis.(17) Among others, low bone marrow concentration of TGF-ÃŽ ² can provide signaling to induce myeloid-biased bone marrow microenvironment. (18) At the molecular level, in aging HSC, TGF-ÃŽ ² regulated genes, such as Nr4a1, Cepba, Jun and Junb were found to be†¦show more content†¦(22) In this context of subclinical mutational carriers, individual patient genetic, epigenetic and immunological variables that govern full acquisition of malignant potential are expected to have predictive and therapeutic im plications. In addition, investigation of clonal adaptive processes especially those associated with pre-MDS/MDS transition could facilitate understanding of disease pathogenesis. 2.2 Mutational analysis Advances in MDS therapy will derive from molecular precision and identification of potential druggable targets for the disease. In 2005, The Cancer Genome Atlas (TCGA), and during 2008, The International Cancer Genome Consortium (ICGC) were designed as large-scale projects to improve understanding of cancer associated recurrent somatic mutations. In AML, robust prognostic relevant mutations were reported with mutational subgroups frequently observed in MDS suggesting similar ability to detect a significant impact on MDS outcome. Seven subgroups including activating signaling, DNA methylation, chromatin modifiers, spliceosome, myeloid transcription factors, tumor suppressor genes, and less commonly observed mutations including cohesin complex, BCOR, and BCORL1 (Fig.3). In this section, we will describe frequency, prognostic and functional implication of