RAR-ALPHA-1 RAR-ALPHA-2-PML MESSENGER-RNA EXPRESSION IN ACUTE PROMYELOCYTIC LEUKEMIA-CELLS - A MOLECULAR AND LABORATORY-CLINICAL CORRELATIVE STUDY/

In addition to the major fusion gene PML-RAR alpha, the t(15;17) in ac ute promyelocytic leukemia (APL) produces the reciprocal fusion gene R AR alpha-FML. To determine the scope of RAR alpha-containing mRNA expr ession in APL cells, we tested PML-RAR alpha-positive APL cells for th e presence of mRNAs initiated from two distinct RAR alpha gene promote rs, alpha 1 and alpha 2. From the normal allele, both RAR alpha 1 and RAR alpha 2 mRNAs were expressed in all APL cases (N = 24), From the t ranslocated allele, RAR alpha 1-PML mRNA was expressed in 77% and RAR alpha 2-PML mRNA in 28% of cases (N = 98). RAR alpha 2-PML mRNA was no t observed in the absence of RAR alpha 1-PML mRNA, There was no associ ation between RAR alpha 1-PML or RAR alpha 2-PML mRNA expression and t he type of PML-RAR alpha mRNA formed by either 5' or 3' breaksites in the PML gene. RAR alpha 1-PML mRNAs and RAR alpha 2-PML mRNAs from 5' PML breaksite cases coded for full-length RAR alpha-PML proteins but R AR alpha 2-PML mRNAs from 3' PML breaksite cases encoded a truncated R AR alpha 2 peptide. RAR alpha 1-alpha 2-PML mRNA expression was not as sociated with differences in APL cell sensitivity to all-trans retinoi c acid(tRA)-induced differentiation in vitro or in clinical outcome af ter tRA or chemotherapy induction therapy (protocol E2491), Our analys is indicated that RAR alpha 1/alpha 2-PML mRNA expression markedly dif fers from normal RAR alpha 1/alpha 2 mRNA expression, that the differe nce in RAR alpha 1-PML and RAR alpha 2-PML mRNA expression frequency i s primarily related to the genomic separation of the RAR alpha 1 and R AR alpha P coding exons, and that variations in RAR alpha 1/alpha 2-PM L mRNA expression likely have no clinically relevant function in APL c ells. (C) 1997 by The American Society of Hematology.