Therapeutically targetable ALK mutations in leukemia

Julia E. Maxson, Monika A. Davare, Samuel B. Luty, Christopher A. Eide, Bill H. Chang, Marc M. Loriaux, Cristina E. Tognon, Daniel Bottomly, Beth Wilmot, Shannon K. McWeeney, Brian J. Druker, Jeffrey W. Tyner

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Genome sequencing is revealing a vast mutational landscape in leukemia, offering new opportunities for treatment with targeted therapy. Here, we identify two patients with acute myelogenous leukemia and B-cell acute lymphoblastic leukemia whose tumors harbor point mutations in the ALK kinase. The mutations reside in the extracellular domain of ALK and are potently transforming in cytokine-independent cellular assays and primary mouse bone marrow colony formation studies. Strikingly, both mutations conferred sensitivity to ALK kinase inhibitors, including the FDA-approved drug crizotinib. On the basis of our results, we propose that tumors harboring ALK mutations may be therapeutically tractable for personalized treatment of certain aggressive leukemias with ALK inhibitors.

Original languageEnglish (US)
Pages (from-to)2146-2150
Number of pages5
JournalCancer Research
Volume75
Issue number11
DOIs
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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