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Cancers 2011, 3(2), 2402-2420; doi:10.3390/cancers3022402

Differentiation Therapy of Acute Myeloid Leukemia

Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137, Poland
* Author to whom correspondence should be addressed.
Received: 30 January 2011 / Revised: 29 April 2011 / Accepted: 5 May 2011 / Published: 16 May 2011
(This article belongs to the Special Issue Cancer Diagnosis and Targeted Therapy)
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Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.
Keywords: acute myeloid leukemia; targeted therapy; differentiation; all-trans retinoic acid; acute promyelocytic leukemia; 1,25-dihydroxyvitamin D3; vitamin D analogs acute myeloid leukemia; targeted therapy; differentiation; all-trans retinoic acid; acute promyelocytic leukemia; 1,25-dihydroxyvitamin D3; vitamin D analogs
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Gocek, E.; Marcinkowska, E. Differentiation Therapy of Acute Myeloid Leukemia. Cancers 2011, 3, 2402-2420.

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