THE SKM-1 LEUKEMIC-CELL LINE ESTABLISHED FROM A PATIENT WITH PROGRESSION TO MYELOMONOCYTIC LEUKEMIA IN MYELODYSPLASTIC SYNDROME (MDS) - CONTRIBUTION TO BETTER UNDERSTANDING OF MDS

Although molecular and cytogenetic studies strongly point to the role of oncogenes, the mechanisms underlying the development of MDS and the ir progressive evolution to AML are still largely unknown. It has been postulated that AML has a preleukemic stage and a multi step pathogen esis, with the preleukemic stem cell able to undergo clonal evolution, with the acquisition of karyotypic abnormalities, leading to the deve lopment of acute leukemic subclones. The activations of the ras oncoge nes or inactivation of the p53 anti-oncogene by point mutations have b een described recently in several cases of MDS as well as AML, suggest ing a critical role for these alterations in the development of these myelogenous leukemias. We reported previously establishment of a leuke mic cell line, SKM-1, from the patient who initially possessed multipl e point mutations of ras genes but lost these mutations during disease progression to myelomonocytic leukemia with acquisition of chromosoma l abnormalities involving the p53 anti-oncogene. This process is chara cterized by genetic instabilities probably due to the failure of their DNA repairment leading to abnormal control of cell proliferation and differentiation. Studying this cell line, SKM-1, is a promising approa ch to understand the mechanisms of the initiation, disease progression , alterations of DNA repairment, and genetic instability in MDS and my elogenous malignancies.