Haema 2012; 3(1): 65-77
by Maria Dimou, Panayiotis Panayiotidis
1st Department of Propaedeutic Medicine, School of Medicine, National and Kapodistrian University of Athens, Greece
Abstract
Chronic Myelogenous Leukemia (CML) is a myeloproliferative disorder which originates from Hemopoietic Stem Cells-HSC carrying the chromosomal translocation t( 9;22). The hallmark of the disease is the production of the fusion gene/protein BCR-ABL which is responsible for the pathogenesis of CML. Tyrosin Kinase Inhibitors-TKIs, target BCR-ABL and have revolutionized the therapy of CML, leading to complete cytogenetic responses and long term survival of patients. In some patients “complete molecular responses” have been obtained ; studies in CML patients who were in “complete molecular response” and discontinued treatment with Imatinib have shown that in the majority of patients a molecular relapse of CML has occurred. This proves that the stem cell population of CML is not eliminated by long term Imatinib therapy. CML stem cells use a variety of biochemical pathways for their survival, autorenewal, inhibition of apoptosis etc. Both Imatinib mesylate and mainly newer TKIs (nilotinib, dastinib etc) lead to deep molecular responses but in vitro studies have shown that they are not able to eliminate the CML HSCs population. Combination studies in CML patients using inhibitors targeting both BCR-ABL and other biochemical pathways present in CML stem cells may lead to “functional cure” in a substantial proportion of CML patients.