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Induction and postremission therapy: new agents

Leukemia volume 17, pages 496–498 (2003)Cite this article

Treatment of acute myeloid leukemia (AML) has not changed in a number of years; so there is a definite need for new therapies. Anthracyclines and cytarabine are still the mainstays of first-line therapy. Novel chemotherapeutic agents, such as temozolomide, an oral alkylating agent, and troxacitabine, a novel nucleotide analog, have been studied, but it is unclear whether they are better than conventional therapy. Gemtuzumab ozogamicin, a novel targeted therapy, may provide benefit in highly selected patients. Arsenic trioxide is efficacious in acute promyelocytic leukemia (APL), but not in other subtypes of leukemia. The successes of all-trans retinoic acid (ATRA) and arsenic trioxide in APL suggest that our goal should be to develop novel therapies to target the specific pathophysiologic processes in AML.

The pathophysiology of AML deals with two issues from the clinician's standpoint. If myelodysplastic syndrome (MDS) is a failure to differentiate because of transcription factor abnormalities, and if chronic myelogenous leukemia (CML), at least in chronic phase, is due to overabundant proliferation resulting from constitutive tyrosine kinase activity, AML involves both problems.1 It would be naïve to think that targeting either one of those two mechanisms by itself will cure the disease, but perhaps aiming at each will begin to approach effective therapy in AML. At least for APL, we currently use chemotherapy to target proliferation and retinoic acid for differentiation, so a multifaceted approach could be feasible in other subtypes of AML. Proliferation can be decreased by inhibiting tyrosine kinases2 and farnesyl transferases,3 as well as by promoting apoptosis. Differentiation can be promoted by hypomethylation of DNA by using DNA methyltransferase inhibitors,4 or histone deacetylase inhibitors,5 and/or manipulating associated phenomena such as drug resistance6 and angiogenesis.7 In addition, immunotherapeutic strategies that do not require as much intrinsic knowledge about the way a cell transforms to a malignant phenotype are also under development.

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  1. Adult Leukemia Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    R M Stone

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This paper is part of a series of keynote addresses to be published in Leukemia. They were presented at the Acute Leukemia Forum, San Fransisco, 19 April 2002. Supported by an unrestricted educational grant from Immunex.

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Stone, R. Induction and postremission therapy: new agents. Leukemia 17, 496–498 (2003). https://doi.org/10.1038/sj.leu.2402864

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