A clinically relevant population of leukemic CD34 -CD38 - cells in acute myeloid leukemia

Jonathan M. Gerber, B Douglas Smith, Brownhilda Ngwang, Hao Zhang, Milada S. Vala, Laura Morsberger, Steven Galkin, Michael I. Collector, Brandy Perkins, Mark J Levis, Constance A. Griffin, Saul J. Sharkis, Michael J Borowitz, Judith Karp, Richard J Jones

Research output: Contribution to journalArticle

Abstract

Relapse of acute myeloid leukemia (AML) is thought to reflect the failure of current therapies to adequately target leukemia stem cells (LSCs), the rare, resistant cells presumed responsible for maintenance of the leukemia and typically enriched in the CD34 +CD38 - cell population. Despite the considerable research on LSCs over the past 2 decades, the clinical significance of these cells remains uncertain. However, if clinically relevant, it is expected that LSCs would be enriched in minimal residual disease and predictive of relapse. CD34 + subpopulations from AML patients were analyzed by flow cytometry throughout treatment. Sorted cell populations were analyzed by fluorescence in situ hybridization for leukemia-specific cytogenetic abnormalities (when present) and by transplantation into immunodeficient mice to determine self-renewal capacity. Intermediate (int) levels of aldehyde dehydrogenase (ALDH) activity reliably distinguished leukemic CD34 +CD38 -cells capable of engrafting immunodeficient mice from residual normal hematopoietic stem cells that exhibited relatively higher ALDH activity. Minimal residual disease detected during complete remission was enriched for the CD34 +CD38 -ALDH int leukemic cells, and the presence of these cells after therapy highly correlated with subsequent clinical relapse. ALDH activity appears to distinguish normal from leukemic CD34 +CD38 - cells and identifies those AML cells associated with relapse.

Original languageEnglish (US)
Pages (from-to)3571-3577
Number of pages7
JournalBlood
Volume119
Issue number15
DOIs
StatePublished - Apr 12 2012

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Gerber, J. M., Smith, B. D., Ngwang, B., Zhang, H., Vala, M. S., Morsberger, L., Galkin, S., Collector, M. I., Perkins, B., Levis, M. J., Griffin, C. A., Sharkis, S. J., Borowitz, M. J., Karp, J., & Jones, R. J. (2012). A clinically relevant population of leukemic CD34 -CD38 - cells in acute myeloid leukemia. Blood, 119(15), 3571-3577. https://doi.org/10.1182/blood-2011-06-364182