Kinstrie, R., Karamitros, D., Goardon, N., Morrison, H., Hamblin, M., Robinson, L., Clark, R. E., Copland, M. and Vyas, P. (2016) Heterogeneous leukemia stem cells in myeloid blast phase chronic myeloid leukemia. Blood Advances, 1(3), pp. 160-169. (doi: 10.1182/bloodadvances.2016000810)
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Abstract
Chronic myeloid leukemia (CML) is an excellent model of the multistep processes in cancer. Initiating BCR-ABL mutations are required for the initial phase of the disease (chronic phase, CP-CML). Some CP-CML patients acquire additional mutation(s) that transforms CP-CML to poor prognosis, hard to treat, acute myeloid or lymphoid leukemia or blast phase CML (BP-CML). It is unclear where in the hemopoietic hierarchy additional mutations are acquired in BP-CML, how the hemopoietic hierarchy is altered as a consequence, and the cellular identity of the resulting leukemia-propagating stem cell (LSC) populations. Here, we show that myeloid BP-CML is associated with expanded populations that have the immunophenotype of normal progenitor populations that vary between patients. Serial transplantation in immunodeficient mice demonstrated functional LSCs reside in multiple populations with the immunophenotype of normal progenitor as well as stem cells. Multicolor fluorescence in situ hybridization detected serial acquisition of cytogenetic abnormalities of chromosome 17, associated with transformation to BP-CML, that is detected with equal frequency in all functional LSC compartments. New effective myeloid BP-CML therapies will likely have to target all these LSC populations.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Morrison, Miss Heather and Kinstrie, Dr Ross and Copland, Professor Mhairi |
| Authors: | Kinstrie, R., Karamitros, D., Goardon, N., Morrison, H., Hamblin, M., Robinson, L., Clark, R. E., Copland, M., and Vyas, P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Blood Advances |
| Publisher: | American Society of Hematology |
| ISSN: | 2473-9529 |
| ISSN (Online): | 2473-9529 |
| Published Online: | 02 December 2016 |
| Copyright Holders: | Copyright © 2016 The American Society of Hematology |
| First Published: | First published in Blood Advances 1(3): 160-169 |
| Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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