Evidence Of Clonality

The neoplastic MDS clone arises from a pluripotent stem cell. The evidence of clonality was originally demonstrated through G6PD mosaicism.13 Subsequently, cyto-genetic studies revealed two clones with and without trisomy eight in patients with sideroblastic anemia.14 Clonality is also supported by restriction fragment length polymorphisms (RFLPs) of X-chromosome genes and by the use of fluorescence in-situ hybridization (FISH).15 The assay is based on differences in X chromosome inactivation patterns between normal and neoplastic tissues of female patients. In a polyclonal cell population, the maternal X chromosome is active in half the cells and inactive in the other half, while in a monoclonal cell population, the maternal X chromosome is either active or inactive in all the cells. This difference in the pattern of X chromosome inactivation between normal and neoplastic cell populations can be demonstrated, in females heterozygous for a particular RFLP, by a Southern blot analysis using X-linked DNA probes with restriction enzymes capable of differentially cleaving the material from the paternal X chromosome on one hand, and the active from the inactive X chromosome on the other. Several studies have also shown evidence of clonality in lymphoid lineages as well, suggesting that the MDS clone arises from early pluripotent stem cells capable of myeloid and lym-phoid differentiation.1617 Karyotypic evolution and complex karyotypic changes may occur with progression of MDS and transformation to AML.

Table 38.1

Altered genes in MDS

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