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RAR 1/RAR 2-PML mRNA Expression in Acute Promyelocytic Leukemia Cells: A Molecular and Laboratory-Clinical Correlative Study
Yun-Ping Li,
Janet Andersen,
Arthur Zelent,
Sreenivas Rao,
Elisabeth Paietta,
Martin S. Tallman,
Peter H. Wiernik, and
Robert E. Gallagher
From the Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY; the Dana Farber Cancer Institute, Boston, MA; the Northwestern University Medical School, Chicago, IL; and the Leukaemia Research Fund, London, UK.
In addition to the major fusion gene PML-RAR , the t(15; 17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RAR -PML. To determine the scope of RAR -containing mRNA expression in APL cells, we tested PML-RAR -positive APL cells for the presence of mRNAs initiated from two distinct RAR gene promoters, 1 and 2. From the normal allele, both RAR 1 and RAR 2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RAR 1-PML mRNA was expressed in 77% and RAR 2-PML mRNA in 28% of cases (N = 98). RAR 2-PML mRNA was not observed in the absence of RAR 1-PML mRNA. There was no association between RAR 1-PML or RAR 2-PML mRNA expression and the type of PML-RAR mRNA formed by either 5' or 3' breaksites in the PML gene. RAR 1-PML mRNAs and RAR 2-PML mRNAs from 5' PML breaksite cases coded for full-length RAR -PML proteins but RAR 2-PML mRNAs from 3' PML breaksite cases encoded a truncated RAR 2 peptide. RAR 1/ 2-PML mRNA expression was not associated with differences in APL cell sensitivity to all-trans retinoic acid(tRA)-induced differentiation in vitro or in clinical outcome after tRA or chemotherapy induction therapy (protocol E2491). Our analysis indicated that RAR 1/ 2-PML mRNA expression markedly differs from normal RAR 1/ 2 mRNA expression, that the difference in RAR 1-PML and RAR 2-PML mRNA expression frequency is primarily related to the genomic separation of the RAR 1 and RAR 2 coding exons, and that variations in RAR 1/ 2-PML mRNA expression likely have no clinically relevant function in APL cells.
Blood, Vol. 90 No. 1 (July 1), 1997:
pp. 306-312
© 1997 by The American Society of Hematology.

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