Supplemental Figure S1 from Therapeutically Targetable ALK Mutations in Leukemia

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

doi:10.1158/0008-5472.22405104.v1

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Supplemental Figure S1 from Therapeutically Targetable ALK Mutations in Leukemia

journal contribution

posted on 2023-03-30, 23:04 authored by 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

ALK is expressed in the B-ALL sample with the ALK A348D mutation.

History

ARTICLE 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. Cancer Res; 75(11); 2146–50. ©2015 AACR.