Characterization of chronic myeloid leukemia stem cells.

Jonathan M. Gerber, L. Qin, Jeanne Kowalski, B Douglas Smith, Constance A. Griffin, Milada S. Vala, Michael I. Collector, Brandy Perkins, Marianna Zahurak, William Matsui, Christopher Gocke, Saul J. Sharkis, Hyam I. Levitsky, Richard J Jones

Research output: Contribution to journalArticle

Abstract

Although tyrosine kinase inhibitors have redefined the care of chronic myeloid leukemia (CML), these agents have not proved curative, likely due to resistance of the leukemia stem cells (LSC). While a number of potential therapeutic targets have emerged in CML, their expression in the LSC remains largely unknown. We therefore isolated subsets of CD34(+) stem/progenitor cells from normal donors and from patients with chronic phase or blast crisis CML. These cell subsets were then characterized based on ability to engraft immunodeficient mice and expression of candidate therapeutic targets. The CD34(+)CD38(-) CML cell population with high aldehyde dehydrogenase (ALDH) activity was the most enriched for immunodeficient mouse engrafting capacity. The putative targets: PROTEINASE 3, SURVIVIN, and hTERT were expressed only at relatively low levels by the CD34(+)CD38(-)ALDH(high) CML cells, similar to the normal CD34(+)CD38(-)ALDH(high) cells and less than in the total CML CD34(+) cells. In fact, the highest expression of these antigens was in normal, unfractionated CD34(+) cells. In contrast, PRAME and WT1 were more highly expressed by all CML CD34(+) subsets than their normal counterparts. Thus, ALDH activity appears to enrich for CML stem cells, which display an expression profile that is distinct from normal stem/progenitor cells and even the CML progenitors. Indeed, expression of a putative target by the total CD34(+) population in CML does not guarantee expression by the LSC. These expression patterns suggest that PROTEINASE 3, SURVIVIN, and hTERT are not optimal therapeutic targets in CML stem cells; whereas PRAME and WT1 seem promising.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalAmerican Journal of Hematology
Volume86
Issue number1
StatePublished - Jan 2011
Externally publishedYes

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Myeloid Progenitor Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Stem Cells
Aldehyde Dehydrogenase
Leukemia
Myeloid Cells
Blast Crisis
Protein-Tyrosine Kinases
Population
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Gerber, J. M., Qin, L., Kowalski, J., Smith, B. D., Griffin, C. A., Vala, M. S., ... Jones, R. J. (2011). Characterization of chronic myeloid leukemia stem cells. American Journal of Hematology, 86(1), 31-37.

Characterization of chronic myeloid leukemia stem cells. / Gerber, Jonathan M.; Qin, L.; Kowalski, Jeanne; Smith, B Douglas; Griffin, Constance A.; Vala, Milada S.; Collector, Michael I.; Perkins, Brandy; Zahurak, Marianna; Matsui, William; Gocke, Christopher; Sharkis, Saul J.; Levitsky, Hyam I.; Jones, Richard J.

In: American Journal of Hematology, Vol. 86, No. 1, 01.2011, p. 31-37.

Research output: Contribution to journalArticle

Gerber, JM, Qin, L, Kowalski, J, Smith, BD, Griffin, CA, Vala, MS, Collector, MI, Perkins, B, Zahurak, M, Matsui, W, Gocke, C, Sharkis, SJ, Levitsky, HI & Jones, RJ 2011, 'Characterization of chronic myeloid leukemia stem cells.', American Journal of Hematology, vol. 86, no. 1, pp. 31-37.
Gerber JM, Qin L, Kowalski J, Smith BD, Griffin CA, Vala MS et al. Characterization of chronic myeloid leukemia stem cells. American Journal of Hematology. 2011 Jan;86(1):31-37.
Gerber, Jonathan M. ; Qin, L. ; Kowalski, Jeanne ; Smith, B Douglas ; Griffin, Constance A. ; Vala, Milada S. ; Collector, Michael I. ; Perkins, Brandy ; Zahurak, Marianna ; Matsui, William ; Gocke, Christopher ; Sharkis, Saul J. ; Levitsky, Hyam I. ; Jones, Richard J. / Characterization of chronic myeloid leukemia stem cells. In: American Journal of Hematology. 2011 ; Vol. 86, No. 1. pp. 31-37.
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