Acute leukemia with promyelocytic features in PML/RARα transgenic mice

Li Zhen He, Carla Tribioli, Roberta Rivi, Daniela Peruzzi, Pier Giuseppe Pelicci, Vera Soares, Giorgio Cattoretti, Pier Paolo Pandolfi

Research output: Contribution to journalArticlepeer-review

Abstract

Acute promyelocytic leukemia (APL) is associated with reciprocal chromosomal translocations involving the retinoic acid receptor α (RARα) locus on chromosome 17. In the majority of cases, RARα translocates and fuses with the promyelocytic leukemia (PML) gene located on chromosome 15. The resulting fusion genes encode the two structurally unique PML/RARα and RARα/PML fusion proteins as well as aberrant PML gene products, the respective pathogenetic roles of which have not been elucidated. We have generated transgenic mice in which the PML/RARα fusion protein is specifically expressed in the myeloid-promyelocytic lineage. During their first year of life, all the PML/RARα transgenic mice have an abnormal hematopoiesis that can best be described as a myeloproliferative disorder. Between 12 and 14 months of age, 10% of them develop a form of acute leukemia with a differentiation block at the promyelocytic stage that closely mimics human APL even in its response to retinoic acid. Our results are conclusive in vivo evidence that PML/RARα plays a crucial role in the pathogenesis of APL.

Original languageEnglish
Pages (from-to)5302-5307
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number10
DOIs
Publication statusPublished - May 13 1997

ASJC Scopus subject areas

  • Genetics
  • General

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