In: Chronic Myeloid Leukemia ISBN: 978-1-62948-971-1 Editors: Celalettin Ustun and Uday R. Popat © 2014 Nova Science Publishers, Inc. Chapter XVIII Can We Cure CML without Transplantation? Prithviraj Bose * , M.D. 1,2 and Pankit Vachhani, M.D. 2 1 Massey Cancer Center and the 2 Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, US Abstract A model disease in many respects, chronic myelogenous leukemia (CML) has been called the pristine paradigm for molecularly targeted therapy. Bcr-Abl tyrosine kinase inhibitors (TKIs) have dramatically altered the therapeutic landscape of CML, so much so that many patients diagnosed in chronic phase and treated appropriately now enjoy a life expectancy similar to that of the general population. However, despite the enormous strides made in advancing therapy for this disease, it remains, for the most part, incurable except by allogeneic hematopoietic stem cell transplantation (HSCT). For patients, this means a lifelong commitment to daily TKI therapy. These agents are expensive, and not without side effects, making cure a highly desirable and worthwhile goal. Multiple studies have shown that in contrast to their impressive efficacy against proliferating CML cells, TKIs are unable to eradicate the tiny fraction of quiescent stem cells that are responsible for disease persistence and recurrence upon TKI discontinuation. This has fueled efforts to better understand CML stem cell biology and elucidate survival pathways unique to these cells, the targeted interruption of which could potentially synergize with Bcr-Abl TKIs to confer synthetic lethality while sparing normal hematopoietic stem cells (HSCs). The molecular pathogenesis of CML and mechanisms of resistance to TKIs are reviewed in detail elsewhere in this volume. In this chapter, we provide a brief overview of these topics, summarize key concepts relating to CML stem cell biology, and discuss strategies to effectively target this difficult-to-kill population that might one day result in a cure for CML. * Address for correspondence: Prithviraj Bose, M.D., McGlothlin Medical Education Center, 1201 E Marshall St, 11 th floor, Room 213, P.O. Box 980070, Richmond, VA 23298, USA. Email: pbose@mcvh-vcu.edu. No part of this digital document may be reproduced, stored in a retrieval system or transmitted commercially in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services.