Heterogeneous leukemia stem cells in myeloid blast phase chronic myeloid leukemia

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:Kinstrie, Dr Ross and Copland, Professor Mhairi and Morrison, Miss Heather
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 > Institute 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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
506531An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandScottish Executive Health Department (SEHHD-CSO)SCD/04RI CANCER SCIENCES
506532An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandBloodwise (BLOODWIS)11017RI CANCER SCIENCES