PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia Journal Article
| Author: | Pandolfi, P. P. |
| Article Title: | PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia |
| 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 α (RARα) 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. RARα 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 RARα 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, RARα 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 understanding of the molecular etiopathogenesis of the disease. Functional analysis of the various fusion proteins as well as RARα partners is revealing strikingly common features beneath a misleading structural heterogeneity which unravels a possible unifying molecular mechanism towards APL leukemogenesis. |
| Keywords: | adult; aged; major clinical study; dna-binding proteins; review; cell maturation; neoplasm proteins; cytogenetics; cell differentiation; transcription factors; nuclear proteins; leukemia, promyelocytic, acute; gene rearrangement; tumor suppressor proteins; acute myeloblastic leukemia; tumor cell; chromosome translocation; translocation, genetic; bone marrow cell; chromosome 11; chromosomes, human, pair 11; receptor gene; chromosome mapping; chromosomes, human, pair 15; apl; humans; human; male; female; chromosome translocations; rarα |
| Journal Title: | Haematologica |
| Volume: | 81 |
| Issue: | 5 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 1996-09-01 |
| Start Page: | 472 |
| End Page: | 482 |
| Language: | English |
| PUBMED: | 8952164 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
Citation Impact
MSK Authors
Related MSK Work