Combination therapy for acute lymphoblastic leukemia


A subset of acute lymphoblastic leukemia (ALL) patients is positive for the Philadelphia chromosome, which is generated by a specific translocation event that causes a fusion between the BCR and ABL1 genes. These patients unfortunately have a poorer prognosis and a more limited response to tyrosine kinase inhibitors that are used to treat other forms of ALL. In this issue of JCI Insight, Charles Mulligan of St. Jude Children's Research Hospital and colleagues show that a combination approach using tyrosine kinase inhibitors and an inhibitor of focal adhesion kinase (FAK) was much more effective in preclinical models of BCR-ABL1+ B-progenitor ALL. They demonstrate that FAK is overexpressed in several models of BCR-ABL1+ ALL and that the FAK inhibitor VS-4718 synergizes with tyrosine inhibitor dasatinib to decrease tumor growth in mouse models. Collectively, their work indicates that a combination approach, targeting both FAK and tyrosine kinases, is a promising treatment strategy for this subset of ALL.



Synergism of FAK and tyrosine kinase inhibition in Ph+ B-ALL


Charles G. Mullighan
St. Jude Children`s Research Hospital
[email protected]

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JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to

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