Therapeutically targetable ALK mutations in leukemia

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

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Leukemia
Mutation
Phosphotransferases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Point Mutation
Acute Myeloid Leukemia
Neoplasms
B-Lymphocytes
Therapeutics
Bone Marrow
Genome
Cytokines
Pharmaceutical Preparations
crizotinib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Therapeutically targetable ALK mutations in leukemia. / Maxson, Julia; Davare, Monika; Luty, Samuel B.; Eide, Christopher A.; Chang, Bill; Loriaux, Marc; Tognon, Cristina E.; Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon; Druker, Brian; Tyner, Jeffrey.

In: Cancer Research, Vol. 75, No. 11, 01.06.2015, p. 2146-2150.

Research output: Contribution to journalArticle

Maxson, Julia ; Davare, Monika ; Luty, Samuel B. ; Eide, Christopher A. ; Chang, Bill ; Loriaux, Marc ; Tognon, Cristina E. ; Bottomly, Daniel ; Wilmot, Beth ; McWeeney, Shannon ; Druker, Brian ; Tyner, Jeffrey. / Therapeutically targetable ALK mutations in leukemia. In: Cancer Research. 2015 ; Vol. 75, No. 11. pp. 2146-2150.
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