Genetic lesions associated with blastic transformation of polycythemia vera and essential thrombocythemia

Gianluca Gaidano, Cristina Pastore, Valeria Santini, Josep Nomdedeu, Barbara Gamberi, Daniela Capello, Federico Vischia, Luigi Resegotti, Umberto Mazza, Pierluigi Rossi Ferrini, Francesco Lo Coco, Giuseppe Saglio

Research output: Contribution to journalArticlepeer-review

Abstract

Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders that may progress to acute leukemia in a subset of patients. This study aimed at investigating the genetic lesions associated with the blastic transformation of PV and ET. A panel of PV and ET cases at different stages of disease was analyzed for the presence of genetic alterations of TP53, NRAS, KRAS, and MDM2 by a combination of mutational analysis and Southern blot hybridization. The occurrence of microsatellite instability (MSI) was also tested in selected cases. Samples of PV and ET analyzed in chronic phase disease were consistently devoid of all genetic lesions tested, suggesting that alterations of TP53, NRAS, KRAS, and MDM2 do not contribute significantly to development of chronic phase PV and ET. Conversely, mutations of TP53 were detected in 7/15 (46.6%) blastic phase cases, including 3/5 PV and 4/10 ET. In blastic phase patients for whom the corresponding chronic phase DNA was also available, it could be documented that the genetic lesion had arisen at the time of blastic transformation. In addition to TP53 mutations, cases of blastic phase PV and ET occasionally harbored mutations of NRAS (one case of blastic phase ET) or displayed MSI (one case of blastic phase PV). These data indicate that inactivation of TP53 is a relatively frequent event associated with the blastic transformation of PV and ET and may be responsible for the tumor progression of these disorders.

Original languageEnglish
Pages (from-to)250-255
Number of pages6
JournalGenes Chromosomes and Cancer
Volume19
Issue number4
DOIs
Publication statusPublished - Aug 1997

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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