Current treatment strategy of acute promyelocytic leukemia

Department of Hematology, Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
Frontiers of Medicine 12/2011; 5(4):341-7. DOI: 10.1007/s11684-011-0169-z
Source: PubMed


Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML). The prognosis of APL has changed from the worst among the AMLs to currently the best. The application of all-trans retinoic acid (ATRA) in the induction therapy of APL decreases the high mortality of newly diagnosed patients, thereby significantly improving the response rate. ATRA combined with anthracycline-based chemotherapy is the current standard treatment, and for high-risk patients, high doses cytarabine have a beneficial effect on relapse prevention. In recent years, the indications of arsenic trioxide (ATO) therapy for APL have been extended from the salvage therapy for relapse patients to the first-line treatment of de novo APL. The introduction of both ATRA and ATO represents great achievements in translational medicine. In this review article, we discuss the therapeutic strategies for this disease, including the initial approaches to newly diagnosed patients, prevention, and treatment of side effects and relapse to ensure the best and timely treatment for each newly diagnosed APL patient.

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    • "In this study, we report for the first time the effects of these natural compounds on ribonucleotide reductase (RR) metabolism in human HL-60 promyelocytic leukemia cells. Acute promyelocytic leukemia is a distinct subtype of acute myeloid leukemia and represents a relatively rare hematological disease, accounting for approximately 5–8% of all AML cases (Mi 2011). The balanced reciprocal translocation t(15;17) generates a PML (promyelocytic leukemia)-RARα (retinoic acid receptor alpha) fusion (onco)gene (Mi et al. 2012). "
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    ABSTRACT: Epigallocatechin gallate (EGCG), ellagic acid (EA) and rosmarinic acid (RA) are natural polyphenols exerting cancer chemopreventive effects. Ribonucleotide reductase (RR; EC converts ribonucleoside diphosphates into deoxyribonucleoside diphosphates being essential for DNA replication, which is why the enzyme is considered an excellent target for anticancer therapy. EGCG, EA, and RA dose-dependently inhibited the growth of human HL-60 promyelocytic leukemia cells, exerted strong free radical scavenging potential, and significantly imbalanced nuclear deoxyribonucleoside triphosphate (dNTP) concentrations without distinctly affecting the protein levels of RR subunits (R1, R2, p53R2). Incorporation of (14)C-cytidine into nascent DNA of tumor cells was also significantly lowered, being equivalent to an inhibition of DNA synthesis. Consequently, treatment with EGCG and RA attenuated cells in the G0/G1 phase of the cell cycle, finally resulting in a pronounced induction of apoptosis. Sequential combination of EA and RA with the first-line antileukemic agent arabinofuranosylcytosine (AraC) synergistically potentiated the antiproliferative effect of AraC, whereas EGCG plus AraC yielded additive effects. Taken together, we show for the first time that EGCG, EA, and RA perturbed dNTP levels and inhibited cell proliferation in human HL-60 promyelocytic leukemia cells, with EGCG and RA causing a pronounced induction of apoptosis. Due to these effects and synergism with AraC, these food ingredients deserve further preclinical and in vivo testing as inhibitors of leukemic cell proliferation. Copyright © 2014 Elsevier GmbH. All rights reserved.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 01/2015; 22(1):213-22. DOI:10.1016/j.phymed.2014.11.017 · 3.13 Impact Factor
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    • "On the other hand, chronic exposure to low-levels of arsenic in drinking water is an emerging risk across different parts of the world, including North America (Figure 1) [4-7]. Paradoxically, arsenic (as arsenic trioxide, A2O3) is also used as therapeutic agent in the treatment of acute promyelocytic leukemia [8,9]. "
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