Gene rearrangements in the molecular pathogenesis of acute promyelocytic leukemia Conference Paper


Authors: Kalantry, S.; Delva, L.; Gaboli, M.; Gandini, D.; Giorgio, M.; Hawe, N.; He, L. Z.; Peruzzi, D.; Rivi, R.; Tribioli, C.; Wang, Z. G.; Zhang, H.; Pandolfi, P. P.
Title: Gene rearrangements in the molecular pathogenesis of acute promyelocytic leukemia
Conference Title: 9th International Conference of the International Society of Differentiation (ISD)
Abstract: Acute Promyelocytic Leukemia (APL) is a distinct subtype of myeloid leukemia that in the USA alone affects more than 3,000 individuals every year. APL is characterized by three distinct and unique features: i) the accumulation in the bone marrow of tumor cells with promyelocytic features; ii) the invariable association with specific translocations which always involve chromosome 17 and the Retinoic Acid Receptor α (RARα) locus; iii) the exquisite sensitivity of APL blasts to the differentiating action of Retinoic Acid (RA). These features have led APL to become the paradigm for therapeutic approaches utilizing differentiating agents. The last 5 years have provided crucial insights into the molecular basis of APL. RARα translocates in 99% of cases to a gene located on chromosome 15 that we initially named myl and subsequently has been called PML. In a few cases, RARα variably translocates to chromosome 11 where it fuses to the PLZF gene or to a newly described partner, NuMA. 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 the comparative analysis of their associated products is crucial for the understanding of the molecular etiopathogenesis of the disease. The generation of animal models, i.e., transgenic mice expressing the fusion genes, will be instrumental in determining the precise contribution of these fusion genes to leukemogenesis. In fact, mice harboring a PML/RARα transgene whose expression is specifically targeted to the myeloid-promyelocytic lineage develop acute myeloid leukemia with promyelocytic features. Moreover, the functional analysis of the various fusion proteins, as well as RARα partners, is revealing striking common features beneath a misleading structural heterogeneity which unravels a possible unifying molecular mechanism towards APL leukemogenesis.
Keywords: gene translocation; pathogenesis; conference paper; cytology; animals; cell division; bone marrow; leukemia, promyelocytic, acute; gene rearrangement; hybrid protein; acute myeloblastic leukemia; gene fusion; hematopoiesis; cell nucleus; molecular biology; zinc finger protein; drug sensitivity; chromosome 11; retinoic acid; chromosome 17; genes, tumor suppressor; retinoic acid receptor; nucleophosmin; genes, neoplasm; chromosome 5; chromosome 15; humans; human; priority journal
Journal Title Journal of Cellular Physiology
Volume: 173
Issue: 2
Conference Dates: 1996 Sep 28-Oct 2
Conference Location: Pisa, Italy
ISBN: 0021-9541
Publisher: John Wiley & Sons, Inc.  
Date Published: 1997-11-01
Start Page: 288
End Page: 296
Language: English
DOI: 10.1002/(sici)1097-4652(199711)173:2<288::aid-jcp38>3.0.co;2-9
PUBMED: 9365539
PROVIDER: scopus
DOI/URL:
Notes: Conference Paper -- Export Date: 17 March 2017 -- Source: Scopus
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MSK Authors
  1. Mirella P Gaboli
    19 Gaboli
  2. Li-Zhen He
    23 He
  3. Roberta Rivi
    25 Rivi
  4. Zhu-Gang   Wang
    17 Wang