Similar expression profiles in CD34+ cells from chronic phase chronic myeloid leukemia patients with and without deep molecular responses to nilotinib

Ami B. Patel, Thoralf Lange, Anthony D. Pomicter, Christopher J. Conley, Christina (Chris) Harrington, Kimberly R. Reynolds, Todd W. Kelley, Thomas O'Hare, Michael W. Deininger

    Research output: Contribution to journalArticle

    Abstract

    The life expectancy of patients with chronic phase chronic myeloid leukemia on tyrosine kinase inhibitor therapy now approaches that of the general population. Approximately 60% of patients treated with second generation tyrosine kinase inhibitors achieve a deep molecular response, the prerequisite for a trial of treatmentfree remission. Those patients unlikely to achieve deep molecular response may benefit from more intensive therapy up front. To identify biomarkers predicting deep molecular response we performed transcriptional profiling on CD34+ progenitor cells from newly diagnosed chronic phase chronic myeloid leukemia patients treated with nilotinib on a prospective clinical trial. Using unsupervised and targeted analytical strategies, we show that gene expression profiles are similar in patients with and without subsequent deep molecular response. This result is in contrast to the distinct expression signature of CD34+ chronic phase chronic myeloid leukemia patients failing to achieve a cytogenetic response on imatinib and suggests that deep molecular response to second-generation tyrosine kinase inhibitors is governed by the biology of more primitive chronic myeloid leukemia cells or extrinsic factors.

    Original languageEnglish (US)
    Pages (from-to)17889-17894
    Number of pages6
    JournalOncotarget
    Volume9
    Issue number25
    DOIs
    StatePublished - Apr 1 2018

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    Leukemia, Myeloid, Chronic Phase
    Protein-Tyrosine Kinases
    Myeloid Cells
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Life Expectancy
    Transcriptome
    Cytogenetics
    4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
    Stem Cells
    Biomarkers
    Clinical Trials
    Therapeutics
    Population

    Keywords

    • BCR-ABL1
    • Chronic myeloid leukemia
    • Deep molecular response
    • Treatment-free remission

    ASJC Scopus subject areas

    • Oncology

    Cite this

    Similar expression profiles in CD34+ cells from chronic phase chronic myeloid leukemia patients with and without deep molecular responses to nilotinib. / Patel, Ami B.; Lange, Thoralf; Pomicter, Anthony D.; Conley, Christopher J.; Harrington, Christina (Chris); Reynolds, Kimberly R.; Kelley, Todd W.; O'Hare, Thomas; Deininger, Michael W.

    In: Oncotarget, Vol. 9, No. 25, 01.04.2018, p. 17889-17894.

    Research output: Contribution to journalArticle

    Patel, Ami B. ; Lange, Thoralf ; Pomicter, Anthony D. ; Conley, Christopher J. ; Harrington, Christina (Chris) ; Reynolds, Kimberly R. ; Kelley, Todd W. ; O'Hare, Thomas ; Deininger, Michael W. / Similar expression profiles in CD34+ cells from chronic phase chronic myeloid leukemia patients with and without deep molecular responses to nilotinib. In: Oncotarget. 2018 ; Vol. 9, No. 25. pp. 17889-17894.
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