Novel Combination Treatments Targeting Chronic Myeloid Leukemia Stem Cells

摘要: Chronic myeloid leukemia (CML) is currently considered incurable in most patients. Stem cell transplantation, an accepted curative option for which extensive experience has been gained, limited by high morbidity and mortality rates, particularly older Tyrosine kinase inhibitors targeting BCR-ABL are widely used induce remission a proportion of patients, but resistance incomplete response to these agents portends eventual relapse disease progression. Although eradicate CML cells, they largely ineffective against the reservoir quiescent leukemic stem cells (LSCs). Thus strong medical need exists therapies that effectively LSCs focus research. To date, evidence obtained from vitro studies, animal models, clinical specimens suggests effective approach may be partner existing with compounds key molecular effectors, including Wnt/β-catenin, hedgehog pathway components, histone deacetylase (HDAC), transforming growth factor-β (TGF-β), Janus 2, promyelocytic protein, arachidonate 5-lipoxygenase (ALOX5). Novel combinations sensitize inhibitors, thereby overcoming creating possibility improving outcome beyond current standard care.