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Targeted Signal Transduction Therapies in Myeloid Malignancies

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Abstract

The myeloid malignancies include the myeloproliferative neoplasms (MPN) including chronic myeloid leukemia (CML), and acute myeloid leukemia (AML). A growing body of evidence documents that these diseases are caused by genetic mutations that constitutively activate tyrosine kinases. They include the BCR/ABL in CML, the V617F JAK2 in Philadelphia chromosome–negative MPN, and the Flt3 ITD and TKD mutations in AML. Trials of the ABL kinase inhibitor, imatinib, have revolutionized the treatment of CML, and there are ongoing studies with other kinase inhibitors in MPN and AML. Here we review results of recent studies with first-generation JAK2 inhibitors in the treatment of MPN and second-generation ABL and Flt3 inhibitors in CML and AML, respectively. It is becoming apparent that although these kinase mutations have similar effects in vitro, each of the diseases has unique features that alter the use of kinase inhibitors in the clinic.

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Disclosure

Dr. Hexner has served as an advisor to Cephalon Oncology. Dr. Carroll receives partial salary support from the United States Veterans Administration. Dr. Carroll receives grant support for research from Sanofi-Aventis, Agios Pharmaceuticals, and TetraLogic Pharmaceuticals. Dr. Carroll has acted as a consultant to Cephalon Oncology. Dr. Perl has no disclosures. Dr. Scott receives partial salary support through the Pfizer Oncology Clinical Fellowship.

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Authors and Affiliations

  1. Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Emma Scott, Elizabeth Hexner, Alexander Perl & Martin Carroll

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  1. Emma Scott
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  2. Elizabeth Hexner
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  3. Alexander Perl
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  4. Martin Carroll
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Correspondence to Martin Carroll.

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Scott, E., Hexner, E., Perl, A. et al. Targeted Signal Transduction Therapies in Myeloid Malignancies. Curr Oncol Rep 12, 358–365 (2010). https://doi.org/10.1007/s11912-010-0126-z

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  • DOI: https://doi.org/10.1007/s11912-010-0126-z

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