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The proportion of CD34+CD38low or neg myeloblasts, but not side population frequency, predicts initial response to induction therapy in patients with newly diagnosed acute myeloid leukemia

Leukemia volume 27, pages 728–731 (2013)Cite this article

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Normal hematopoiesis is sustained by a relatively small pool of self-renewing primitive hematopoietic stem cells (HSCs). In murine hematopoietic repopulation studies, human cells with bright expression of CD34, but no expression of CD38, are highly enriched in HSC activity.1 Cells with similar immunophenotype are implicated as leukemia stem cells (LSCs),2 the initiating and repopulating reservoir for acute myeloid leukemia (AML). CD34+CD38neg cell frequency at diagnosis correlates with the incidence of minimal residual disease following achievement of complete remission (CR) in adult AML3 and with worse event-free survival in pediatric AML.4 A similar, but not identical, population of cells known as ‘side population’ (SP) has been defined based on ability to efflux fluorescent dye Hoechst 33342 via the ABCG2 multidrug resistance-mediating transporter that can be inhibited by fungal toxin Fumitremorgin C (FumC).5 The SP was originally characterized in mice6 and was demonstrated to contain primitive HSCs. The stem cell reservoir in nearly all normal tissues resides in the SP,7 and it also contains the primitive stem cells for solid tumors, including breast, prostate and lung cancer.8, 9, 10

The relationship between SP and CD34+CD38dim cells has not been previously explored in AML. Three studies demonstrated that SP could be isolated from AML patients. The first study of 16 patients showed that presence of the SP was not related to expression of the multidrug resistance gene (MDR-1), expressed variable CD38, was present with different types of cytogenetics abnormalities, and variably engrafted immunodeficient mice.11 The second study demonstrated that the SP was present in 80% of 61 patients, that 3 out of 28 cases could engraft NODscid mice and that 11/11 exhibited abnormal cytogenetics.12 The third study highlighted the heterogeneity of the SP derived from 48 patients, although there was uniform expression of the stem cell marker CLL-1.13

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Acknowledgements

This project was supported by a grant from the Leukemia and Lymphoma Society Translational Research Program (to PSB). We thank Ms Caroline Stamato for her assistance with the manuscript.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Weill-Cornell Medical College, New York, NY, USA

    M Roshal

  2. Division of Hematology, Department of Medicine, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA

    S Chien, E H Estey, T Papayannopoulou & P S Becker

  3. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    M Othus

  4. Seattle Cancer Care Alliance, Seattle, WA, USA

    B L Wood & M Fang

  5. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    M Fang, F R Appelbaum & E H Estey

  6. Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA

    F R Appelbaum

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Correspondence to P S Becker.

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Roshal, M., Chien, S., Othus, M. et al. The proportion of CD34+CD38low or neg myeloblasts, but not side population frequency, predicts initial response to induction therapy in patients with newly diagnosed acute myeloid leukemia. Leukemia 27, 728–731 (2013). https://doi.org/10.1038/leu.2012.217

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