A retrovirus carrying the promyelocyte-retinoic acid receptor PML-RARalpha fusion gene transforms haematopoietic progenitors in vitro and induces acute leukaemias

Muriel Altabef (1, 2) , Madeleine Garcia (1, 2) , Catherine Lavau (3) , Suk-Chul Bae (1, 2) , Anne Dejean (3) , Jacques Samarut (1, 2)

1 CNRS - Centre National de la Recherche Scientifique
2 ENS de Lyon - École normale supérieure de Lyon
3 Recombinaison et Expression Génétique

The promyelocyte (PML)-retinoic acid receptor alpha (RARalpha) fusion gene results from a t(15;17) chromosome translocation in acute promyelocytic leukaemia. We have analysed the oncogenic potential of the human fusion PML-RARalpha product in chicken using retrovirus vectors. We show that PML-RARalpha transforms very early haematopoietic progenitor cells in vitro and induces acute leukaemias. Neither PML nor RARalpha domains alone achieve such a transformation. The PML-RARalpha viruses recovered from the transformed cells carry two point mutations in the PML domain, one of which alters both the pattern of intracellular localization of the fusion protein and its functional interference with AP-1, thus defining an essential domain in PML for oncogenic transformation.

Keywords: haematopoietic differentiation; leukaemic transformation; nuclear hormone receptor; PML-RARa

Domains: Life Sciences [q-bio]

Muriel Altabef, Madeleine Garcia, Catherine Lavau, Suk-Chul Bae, Anne Dejean, et al.. A retrovirus carrying the promyelocyte-retinoic acid receptor PML-RARalpha fusion gene transforms haematopoietic progenitors in vitro and induces acute leukaemias. EMBO Journal, 1996, 15 (11), pp.2707-16. ⟨10.1002/j.1460-2075.1996.tb00631.x⟩. ⟨pasteur-03238257⟩