Effect of the acute promyelocytic leukemia PML/RARα protein on differentiation and survival of myleoid precursors

Marta Fagioli, Francesco Grignani, Pier Francesco Ferrucci, Myriam Alcalay, Amedea Mencarelli, Lldo Nicoletti, Fausto Grignani, Pier Giuseppe Pelicci

Research output: Contribution to journalArticle

Abstract

Acute promyelocytic leukaemia is characterized by an expansion of haematopoietic precursors arrested at the promyelocytic stage (1). The differentiation block can be reversed by retinoic acid, which induces blast differentiation both in vitro (2) and in vivo (3-4). Acute promyelocytic leukaemia is also characterized by a 15;17 chromosome translocation (5) with breakpoints within the retinoic acid alpha receptor (RARα) gene on 17 and within the PML gene, that encodes a putative transcription factor of unknown function (6-7), on 15 (8-10). As a consequence of the translocation a PML/RARα gene is formed. It is trascriptionally active and encodes a PML/RARα fusion protein detectable in all APL cases (11-14). We expressed the PML/RARα protein in U937 myeloid precursor cell line and show that they: i) lose the capacity to differentiate under the action of different stimuli (vitamin D3, transforming growth factor β1); ii) acquire enhanced sensitivity to retinoic acid; iii) exhibit a higher growth rate that is due to a reduction in apoptotic cell death. These results provide the first evidence of biological activity of PML/RARα and recapitulate critical features of the promyelocytic leukaemia phenotype.

Original languageEnglish
JournalLeukemia
Volume8
Issue numberSUPPL.1
Publication statusPublished - 1994

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Acute Promyelocytic Leukemia
Tretinoin
Proteins
Genes
Chromosomes, Human, Pair 5
U937 Cells
Cholecalciferol
Transforming Growth Factors
Myeloid Cells
Leukemia
Cell Death
Transcription Factors
Retinoic Acid Receptor alpha
Phenotype
Cell Line
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

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Effect of the acute promyelocytic leukemia PML/RARα protein on differentiation and survival of myleoid precursors. / Fagioli, Marta; Grignani, Francesco; Ferrucci, Pier Francesco; Alcalay, Myriam; Mencarelli, Amedea; Nicoletti, Lldo; Grignani, Fausto; Pelicci, Pier Giuseppe.

In: Leukemia, Vol. 8, No. SUPPL.1, 1994.

Research output: Contribution to journalArticle

Fagioli, Marta ; Grignani, Francesco ; Ferrucci, Pier Francesco ; Alcalay, Myriam ; Mencarelli, Amedea ; Nicoletti, Lldo ; Grignani, Fausto ; Pelicci, Pier Giuseppe. / Effect of the acute promyelocytic leukemia PML/RARα protein on differentiation and survival of myleoid precursors. In: Leukemia. 1994 ; Vol. 8, No. SUPPL.1.
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