Research ArticleLEUKEMIA

Synthetic lethality of TNK2 inhibition in PTPN11-mutant leukemia

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Science Signaling  17 Jul 2018:
Vol. 11, Issue 539, eaao5617
DOI: 10.1126/scisignal.aao5617

A ready-to-go treatment for AML and JMML

In some acute myeloid and juvenile myelomonocytic leukemias (AML and JMML, respectively), tumor growth is driven by activating mutations in the phosphatase PTPN11. Jenkins et al. found that mutant PTPN11 activity is enhanced by the kinase TNK2. The multikinase inhibitor dasatinib decreased the activity of TNK2, mutant PTPN11, and downstream proliferative pathways in patient cells in culture; decreased their growth in murine bone marrow cocultures; and extended survival in a patient with PTPN11-mutant JMML. Although dasatinib does not block mutant PTPN11 activity entirely, it is clinically approved for the treatment of other leukemias (CML and ALL), suggesting that its use could be extended to AML and JMML to slow disease progression in patients.

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