Targeting myelogenous leukemia stem cells: role of the circulation
- Hematology/Oncology Division, University of Rochester, Rochester, NY, USA
Unlike stem cells from solid tumors, the stem cells which initiate myelogenous leukemias arise in marrow, an organ with a unique circulation which allows ready access of leukemia cells, including leukemia stem cells (LSCs), to the vasculature. This poses unique problems in the targeting of LSCs since these cells are found circulating in the majority of leukemia cases at diagnosis and are usually not detectable during remission states. Because most cases of leukemia relapse, it is suggested that LSCs remain quiescent in the marrow until they eventually proliferate and circulate again. This indicates that effective targeting of LSCs must occur not only in peripheral circulation but in the micro-circulation of the marrow. Targeting such interactions may overcome cell adhesion-mediated treatment resistance, other multi-drug resistance mechanisms, and opportunities for clonal evolution in the marrow environment. Targeting selectins and integrins, signal transduction mediators, and chemokine/cytokine networks in the marrow micro-circulation may aid in abrogating leukemia-initiating stem cells which contribute to disease relapse. LSCs possess surface antigen profiles and signal transduction activation profiles which may allow differential targeting as compared with normal hematopoietic stem cells.
Keywords: leukemia stem cells, antibody, signal transduction, vascular interactions, targeting
Citation: Liesveld J (2012) Targeting myelogenous leukemia stem cells: role of the circulation.Front. Oncol. 2:86. doi:10.3389/fonc.2012.00086
Received: 11 June 2012; Paper pending published: 22 June 2012;
Accepted: 16 July 2012; Published online: 02 August 2012.
Edited by:Michael R. King, Cornell University, USA
Reviewed by:Joel Wojciechowski, Balance Engineering LLC, USA
Srinivas Narasipura, Rush University, USA
Copyright: © 2012 Liesveld. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Jane Liesveld, Hematology/Oncology Division, University of Rochester, Box 704, 601 Elmwood Avenue, Rochester, NY, USA.e-mail:firstname.lastname@example.org