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Acute Promyelocytic Leukemia
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) and is treated differently than other types of AML. Optimal treatment requires rapid initiation of treatment and supportive care measures.[1] The characteristic chromosomal abnormality associated with APL is t(15;17). This translocation involves a breakpoint that includes the retinoid acid receptor and that leads to production of the promyelocytic leukemia/retinoic acid receptor alpha (PML/RARA) fusion protein.[2]
Clinically, APL is commonly characterized by a severe coagulopathy often present at the time of diagnosis.[3] Mortality during induction (with cytotoxic agents) due to bleeding complications is more common in this subtype than in other French-American-British classifications. Because of the extremely low incidence of central nervous system disease in patients with APL, a lumbar puncture is not required at the time of diagnosis and prophylactic intrathecal chemotherapy is not administered. Studies have demonstrated that the absence of PML/RARA RNA chimeric transcript expression at the end of therapy, as detected by reverse-transcription–polymerase chain reaction monitoring, predicts a low risk of relapse.[4,5,6]
The leukemia cells from patients with APL are especially sensitive to the differentiation-inducing effects of all-trans retinoic acid (ATRA). The basis for the dramatic efficacy of ATRA. against APL is the ability of pharmacologic doses of ATRA to overcome the repression of signaling caused by the PML/RARA fusion protein at physiologic ATRA concentrations. Restoration of signaling leads to differentiation of APL cells and then to postmaturation apoptosis.[7] Most patients with APL achieve a complete remission (CR) when treated with ATRA, though single-agent ATRA is generally not curative.[8,9] A series of randomized clinical trials has defined the benefit of combining ATRA with chemotherapy during induction therapy and also the utility of using ATRA as maintenance therapy.[10,11,12] For children with APL, survival rates exceeding 80% are now achievable using treatment programs that prescribe the rapid initiation of ATRA and appropriate supportive care measures.[1,13,14,15]
Molecular variants of APL produce fusion proteins that join distinctive gene partners (e.g., PLZF, NPM, STAT5B, and NuMA) to RARA.[16] Recognition of these rare variants is important as they differ in their sensitivity to ATRA and to arsenic trioxide.[17] The PLZF-RARA variant, characterized by t(11;17)(q23q21), represents about 0.8% of APL, expresses surface CD56 and has very fine granules compared with t(15;17) APL.[18,19,20] APL with PLZF-RARA has been associated with a poor prognosis and does not usually respond to ATRA or to arsenic trioxide.[17,18,19,20] The rare APL variants with NPM-RARA [t(5;17)(q35,q21)] or with NuMA-RARA [t(11;17)(q13,q21)] translocations are responsive to ATRA.[17,21,22,23,24]
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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER
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