Molecular Mechanism for Chromosomal Translocation in Human Leukmia

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It is well known that Topoisomerase II inhibitor often causes treatment related leukemia in human. We have demonstrated genomic instability such as a deficiency of ATM is involved in chromosomal translocation and leads to leukemia. We have been interested in recapitulating this phenomenon in human cord blood cells. For this purpose we have successfully constructed renti-virus siRNA system for human ATM, enabling us to proceed this project to further step. We have also conducted a study on how often the human cord blood cells have aberrant clones with regard to gene expression of differentiation-associated markers. In 28 cords blood samples we have identified 9 samples have an apparent abnormal clones. Among 9 samples 5 were characterized by the expression of CD34+CD7+CD45w+, while 4 were by CD34+CD20+CD45+. The clones with CD34+CD7+CD45w+ were recently shown to correspond to precursor NK cells. We are now in the process on the molecular and cytogenetical characterization of these abnormal clones.We have recently identified XAB2 as a co repressor protein. When cells express high amount of XAB2, cells became resistant to differentiation induction by Retinoic Acid. This is a novel molecule which is involved in the maintenance of immaturity of hemopoietic stem cells and we speculate this protein is also involved the chromosomal translocation of hemopoietic stem cells.