[MOL] AAMJ ABSTRATS: Management of acute promyelocytic leukemia.... [03007] Medicine On Line

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[MOL] AAMJ ABSTRATS: Management of acute promyelocytic leukemia....

Current issues in the management of acute promyelocytic leukemia.

Slack JL, Rusiniak ME

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. James.Slack@RoswellPark.org

[Medline record in process]

Acute promyelocytic leukemia (APL) is caused by one of four genetic lesions that disrupt the alpha receptor for retinoic acid, RAR alpha. The fusion protein responsible for greater than 99% of APL cases, PML-RAR alpha, inhibits PML-dependent apoptotic pathways in a dominant negative fashion and blocks myeloid differentiation by direct transcriptional inhibition of retinoic acid target genes. This transcriptional inhibition is mediated by recruitment of co-repressor proteins and resultant deacetylation of histones in the promoter regions of genes (yet to be identified) that control promyelocyte development. In the presence of high levels of all-trans retinoic acid (ATRA), both PML-dependent apoptotic mechanisms and myeloid-specific gene expression programs are reactivated. In the clinic, the combination of anthracycline-based chemotherapy plus ATRA cures approximately 80% of APL patients, and a high percentage of relapsed patients can achieve second remissions with arsenic trioxide. With the publication of results from the European APL 93 trial, the 'standard-of-care' for induction treatment of APL now includes ATRA plus concurrent anthracycline-based chemotherapy. The amount and type of consolidation therapy necessary for an individual APL patient remains somewhat of an open question, but at present should include at least two cycles of chemotherapy. Based on recent trials that demonstrate a benefit of maintenance ATRA ( low-dose chemotherapy), all APL patients should probably receive some type of maintenance therapy. While the above approach currently cures the majority of APL patients, future improvements in the treatment of this disease will require risk-adapted protocols that incorporate real-time molecular monitoring and appropriate introduction of novel therapeutic agents.

PMID: 10870476, UI: 20328543
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