Gefitinib đạt được sự thuyên giảm hoàn toàn về mặt hình thái học trong bệnh bạch cầu myeloid cấp tính có đột biến ALK – Nature

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The cytogenetic abnormality inv(2)(p23q13) in acute myeloid leukemia (AML) results in a fusion of RANBP2 with ALK. This fusion makes ALK constitutively active and acts as a driver for the proliferation of AML cell lines. Gilteritinib, a FLT3 inhibitor approved in AML, also can inhibit ALK among other receptor tyrosine kinases. A 75-year-old-woman with a history of essential thrombocythemia (ET) and a presumed germline DDX41 mutation developed ALK-fusion positive AML and despite standard therapies was transfusion-dependent and globally declining. The patient has been on gilteritinib with an ongoing response of more than one year with near normal blood counts and no evidence of AML. The fact that she was found to harbor a presumed germline DDX41 alteration may account for why she developed, and yet survived, two myeloid neoplasms (ET and AML). Additionally, this demonstrates that gilteritinib is clinically active as an ALK inhibitor, and could be considered for use in any AML patient presenting with an inv(2(p23q13)) translocation. Finally, it is an example of using a disease-agnostic, precision medicine approach to arrive at a beneficial treatment.