PMID: 8952164Sep 1, 1996Paper

PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia

Haematologica
P P Pandolfi

Abstract

Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia that in the USA and Italy alone affects more than 3,000 individuals every year. APL is characterized by three distinct and unique features: i) accumulation in the bone marrow of tumor cells with promyelocytic features; ii) invariable association with specific translocations which always involve chromosome 17 and the retinoic acid receptor alpha (RAR alpha) locus; iii) exquisite sensitivity of APL blasts to the differentiating action of retinoic acid (RA). From this point of view APL has become the paradigm for therapeutic approaches utilizing differentiating agents. The last five years have been crucial for the understanding of the molecular basis of APL. RAR alpha translocates in 99% of cases to a gene located on chromosome 15 that we initially named myl and is now known as PML. In a few cases RAR alpha variably translocates to chromosome 11, where it fuses to the PLZF gene or to a gene, also on 11, which has not yet been characterized. In addition, RAR alpha is also found translocated to chromosome 5, where it fuses to the NPM gene. The cloning of variant translocations in APL and comparative analysis of their associated products is crucial for the u...Continue Reading

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