RARα1/RARα2-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 M. Paietta, Martin S. Tallman, Peter H. Wiernik, Robert E. Gallagher

Research output: Contribution to journalArticle

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Abstract

In addition to the major fusion gene PML-RARα, the t(15;17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RARα-PML. To determine the scope of RARα containing mRNA expression in APL cells, we tested PML-RARα-positive APL cells for the presence of mRNAs initiated from two distinct RARα gene promoters, α1 and α2. From the normal allele, both RARα1 and RARα2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RARα1-PML mRNA was expressed in 77% and RARα2-PML mRNA in 28% of cases (N = 98). RAR2α2-PML mRNA was not observed in the absence of RARα1-PML mRNA. There was no association between RARα1-PML or RARα2-PML mRNA expression and the type of PML-RARα mRNA formed by either 5' or 3' breaksites in the PML gene. RARα1-PML mRNAs and RARα2-PML mRNAs from 5' PML breaksite cases coded for full-length RARα-PML proteins but RARα2-PML mRNAs from 3' PML breaksite cases encoded a truncated RARα2 peptide. RARα1/α2- 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 RARα1/α2-PML mRNA expression markedly differs from normal RARα1/α2 mRNA expression, that the difference in RARα1-PML and RARα2-PML mRNA expression frequency is primarily related to the genomic separation of the RARα1 and RARα2 coding exons, and that variations in RARα1/α2-PML mRNA expression likely have no clinically relevant function in APL cells.

Original languageEnglish (US)
Pages (from-to)306-312
Number of pages7
JournalBlood
Volume90
Issue number1
StatePublished - Jul 1 1997
Externally publishedYes

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Clinical laboratories
Acute Promyelocytic Leukemia
Messenger RNA
Genes
Clinical Studies
Gene Fusion
Tretinoin
Fusion reactions
Alleles
Induction Chemotherapy

ASJC Scopus subject areas

  • Hematology

Cite this

Li, Y. P., Andersen, J., Zelent, A., Rao, S., Paietta, E. M., Tallman, M. S., ... Gallagher, R. E. (1997). RARα1/RARα2-PML mRNA expression in acute promyelocytic leukemia cells: A molecular and laboratory-clinical correlative study. Blood, 90(1), 306-312.

RARα1/RARα2-PML mRNA expression in acute promyelocytic leukemia cells : A molecular and laboratory-clinical correlative study. / Li, Yun Ping; Andersen, Janet; Zelent, Arthur; Rao, Sreenivas; Paietta, Elisabeth M.; Tallman, Martin S.; Wiernik, Peter H.; Gallagher, Robert E.

In: Blood, Vol. 90, No. 1, 01.07.1997, p. 306-312.

Research output: Contribution to journalArticle

Li, YP, Andersen, J, Zelent, A, Rao, S, Paietta, EM, Tallman, MS, Wiernik, PH & Gallagher, RE 1997, 'RARα1/RARα2-PML mRNA expression in acute promyelocytic leukemia cells: A molecular and laboratory-clinical correlative study', Blood, vol. 90, no. 1, pp. 306-312.
Li, Yun Ping ; Andersen, Janet ; Zelent, Arthur ; Rao, Sreenivas ; Paietta, Elisabeth M. ; Tallman, Martin S. ; Wiernik, Peter H. ; Gallagher, Robert E. / RARα1/RARα2-PML mRNA expression in acute promyelocytic leukemia cells : A molecular and laboratory-clinical correlative study. In: Blood. 1997 ; Vol. 90, No. 1. pp. 306-312.
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abstract = "In addition to the major fusion gene PML-RARα, the t(15;17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RARα-PML. To determine the scope of RARα containing mRNA expression in APL cells, we tested PML-RARα-positive APL cells for the presence of mRNAs initiated from two distinct RARα gene promoters, α1 and α2. From the normal allele, both RARα1 and RARα2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RARα1-PML mRNA was expressed in 77{\%} and RARα2-PML mRNA in 28{\%} of cases (N = 98). RAR2α2-PML mRNA was not observed in the absence of RARα1-PML mRNA. There was no association between RARα1-PML or RARα2-PML mRNA expression and the type of PML-RARα mRNA formed by either 5' or 3' breaksites in the PML gene. RARα1-PML mRNAs and RARα2-PML mRNAs from 5' PML breaksite cases coded for full-length RARα-PML proteins but RARα2-PML mRNAs from 3' PML breaksite cases encoded a truncated RARα2 peptide. RARα1/α2- 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 RARα1/α2-PML mRNA expression markedly differs from normal RARα1/α2 mRNA expression, that the difference in RARα1-PML and RARα2-PML mRNA expression frequency is primarily related to the genomic separation of the RARα1 and RARα2 coding exons, and that variations in RARα1/α2-PML mRNA expression likely have no clinically relevant function in APL cells.",
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AU - Rao, Sreenivas

AU - Paietta, Elisabeth M.

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AU - Wiernik, Peter H.

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N2 - In addition to the major fusion gene PML-RARα, the t(15;17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RARα-PML. To determine the scope of RARα containing mRNA expression in APL cells, we tested PML-RARα-positive APL cells for the presence of mRNAs initiated from two distinct RARα gene promoters, α1 and α2. From the normal allele, both RARα1 and RARα2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RARα1-PML mRNA was expressed in 77% and RARα2-PML mRNA in 28% of cases (N = 98). RAR2α2-PML mRNA was not observed in the absence of RARα1-PML mRNA. There was no association between RARα1-PML or RARα2-PML mRNA expression and the type of PML-RARα mRNA formed by either 5' or 3' breaksites in the PML gene. RARα1-PML mRNAs and RARα2-PML mRNAs from 5' PML breaksite cases coded for full-length RARα-PML proteins but RARα2-PML mRNAs from 3' PML breaksite cases encoded a truncated RARα2 peptide. RARα1/α2- 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 RARα1/α2-PML mRNA expression markedly differs from normal RARα1/α2 mRNA expression, that the difference in RARα1-PML and RARα2-PML mRNA expression frequency is primarily related to the genomic separation of the RARα1 and RARα2 coding exons, and that variations in RARα1/α2-PML mRNA expression likely have no clinically relevant function in APL cells.

AB - In addition to the major fusion gene PML-RARα, the t(15;17) in acute promyelocytic leukemia (APL) produces the reciprocal fusion gene RARα-PML. To determine the scope of RARα containing mRNA expression in APL cells, we tested PML-RARα-positive APL cells for the presence of mRNAs initiated from two distinct RARα gene promoters, α1 and α2. From the normal allele, both RARα1 and RARα2 mRNAs were expressed in all APL cases (N = 24). From the translocated allele, RARα1-PML mRNA was expressed in 77% and RARα2-PML mRNA in 28% of cases (N = 98). RAR2α2-PML mRNA was not observed in the absence of RARα1-PML mRNA. There was no association between RARα1-PML or RARα2-PML mRNA expression and the type of PML-RARα mRNA formed by either 5' or 3' breaksites in the PML gene. RARα1-PML mRNAs and RARα2-PML mRNAs from 5' PML breaksite cases coded for full-length RARα-PML proteins but RARα2-PML mRNAs from 3' PML breaksite cases encoded a truncated RARα2 peptide. RARα1/α2- 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 RARα1/α2-PML mRNA expression markedly differs from normal RARα1/α2 mRNA expression, that the difference in RARα1-PML and RARα2-PML mRNA expression frequency is primarily related to the genomic separation of the RARα1 and RARα2 coding exons, and that variations in RARα1/α2-PML mRNA expression likely have no clinically relevant function in APL cells.

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