Association of acute myeloid leukemia’s most immature phenotype with risk groups and outcomes

Jonathan M. Gerber, Joshua F. Zeidner, Sarah Morse, Amanda L. Blackford, Brandy Perkins, Breann Yanagisawa, Hao Zhang, Laura Morsberger, Judith Karp, Yi Ning, Christopher Gocke, Gary Rosner, B Douglas Smith, Richard J Jones

Research output: Contribution to journalArticle

Abstract

The precise phenotype and biology of acute myeloid leukemia stem cells remain controversial, in part because the “gold standard” immunodeficient mouse engraftment assay fails in a significant fraction of patients and identifies multiple cell-types in others. We sought to analyze the clinical utility of a novel assay for putative leukemia stem cells in a large prospective cohort. The leukemic clone’s most primitive hematopoietic cellular phenotype was prospectively identified in 109 newly-diagnosed acute myeloid leukemia patients, and analyzed against clinical risk groups and outcomes. Most (80/109) patients harbored CD34+CD38- leukemia cells. The CD34+CD38- leukemia cells in 47 of the 80 patients displayed intermediate aldehyde dehydrogenase expression, while normal CD34+CD38- hematopoietic stem cells expressed high levels of aldehyde dehydrogenase. In the other 33/80 patients, the CD34+CD38- leukemia cells exhibited high aldehyde dehydrogenase activity, and most (28/33, 85%) harbored poor-risk cytogenetics or FMS-like tyrosine kinase 3 internal tandem translocations. No CD34+ leukemia cells could be detected in 28/109 patients, including 14/21 patients with nucleophosmin-1 mutations and 6/7 acute promyelocytic leukemia patients. The patients with CD34+CD38- leukemia cells with high aldehyde dehydrogenase activity manifested a significantly lower complete remission rate, as well as poorer event-free and overall survivals. The leukemic clone’s most immature phenotype was heterogeneous with respect to CD34, CD38, and ALDH expression, but correlated with acute myeloid leukemia risk groups and outcomes. The strong clinical correlations suggest that the most immature phenotype detectable in the leukemia might serve as a biomarker for “clinically- relevant” leukemia stem cells. ClinicalTrials.gov: NCT01349972.

Original languageEnglish (US)
Pages (from-to)607-616
Number of pages10
JournalHaematologica
Volume101
Issue number5
DOIs
StatePublished - Apr 30 2016

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Acute Myeloid Leukemia
Leukemia
Phenotype
Aldehyde Dehydrogenase
Stem Cells
Clone Cells
Myeloid Progenitor Cells
Acute Promyelocytic Leukemia
Hematopoietic Stem Cells
Cytogenetics
Protein-Tyrosine Kinases
Disease-Free Survival
Biomarkers
Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

Gerber, J. M., Zeidner, J. F., Morse, S., Blackford, A. L., Perkins, B., Yanagisawa, B., ... Jones, R. J. (2016). Association of acute myeloid leukemia’s most immature phenotype with risk groups and outcomes. Haematologica, 101(5), 607-616. https://doi.org/10.3324/haematol.2015.135194

Association of acute myeloid leukemia’s most immature phenotype with risk groups and outcomes. / Gerber, Jonathan M.; Zeidner, Joshua F.; Morse, Sarah; Blackford, Amanda L.; Perkins, Brandy; Yanagisawa, Breann; Zhang, Hao; Morsberger, Laura; Karp, Judith; Ning, Yi; Gocke, Christopher; Rosner, Gary; Smith, B Douglas; Jones, Richard J.

In: Haematologica, Vol. 101, No. 5, 30.04.2016, p. 607-616.

Research output: Contribution to journalArticle

Gerber JM, Zeidner JF, Morse S, Blackford AL, Perkins B, Yanagisawa B et al. Association of acute myeloid leukemia’s most immature phenotype with risk groups and outcomes. Haematologica. 2016 Apr 30;101(5):607-616. https://doi.org/10.3324/haematol.2015.135194
Gerber, Jonathan M. ; Zeidner, Joshua F. ; Morse, Sarah ; Blackford, Amanda L. ; Perkins, Brandy ; Yanagisawa, Breann ; Zhang, Hao ; Morsberger, Laura ; Karp, Judith ; Ning, Yi ; Gocke, Christopher ; Rosner, Gary ; Smith, B Douglas ; Jones, Richard J. / Association of acute myeloid leukemia’s most immature phenotype with risk groups and outcomes. In: Haematologica. 2016 ; Vol. 101, No. 5. pp. 607-616.
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