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From DNA Sequencing to Clinical Trials: Finding New Targeted Drugs for Acute Myeloid Leukemia

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Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by clonal expansion of myeloid progenitor cells, resulting in disturbed hematopoiesis and bone marrow failure. For decades, AML therapy was relatively straightforward: clinicians assessed whether the patient was fit or unfit for standard chemotherapy and selected the treatment from among limited choices. With the advent of high-throughput sequencing technologies, significant progress has been made in unraveling the AML genome and understanding leukemogenesis driven by recurrent mutations in signaling and kinase pathways, DNA methylation, and spliceosome complex genes. We are now poised to see our research-based advances translate clinically into the treatment of patients with AML. As recently as within the last 2 years, the United States Food and Drug Administration (FDA) approved eight novel therapies for patients with AML. In this review, we discuss recently approved agents targeting fms-like tyrosine kinase 3 (FLT3), isocitrate dehydrogenase (IDH), B-cell lymphoma-2 (BCL-2), and other promising novel AML agents that are in late stages of clinical development.

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  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Musa Yilmaz & Naval Daver

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  1. Musa Yilmaz
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Correspondence to Naval Daver.

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Naval Daver has received research funding from: Pfizer, BMS, Novartis, Daiichi-Sankyo, Karyopharm, Incyte, Abbvie, Servier, Genentech, Nohla, Glymomimeticsm Immunogen; Advisory/Consulting: Prizer, Novartis, BMS, Otsuka, Celgene, Incyte, Jazz, Karyopharm, Sunesis, Immunogen, Abbvie, Astellas, Daiichi-Sankyo, Agio; Honoraria: BMS, Jazz, Novartis, Incyte, Otsuka, Immunogen, Pfizer, Astellas, Abbvie. Musa Yilmaz declares no conflicts of interest that might be relevant to the contents of this article.

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Yilmaz, M., Daver, N. From DNA Sequencing to Clinical Trials: Finding New Targeted Drugs for Acute Myeloid Leukemia. Drugs 79, 1177–1186 (2019). https://doi.org/10.1007/s40265-019-01144-7

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