Association of PML-RARα fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia

An intergroup molecular study

Robert E. Gallagher, Cheryl L. Willman, James L Slack, Janet W. Andersen, Yun Ping Li, David Viswanatha, Clara D. Bloomfield, Frederick R. Appelbaum, Charles A. Schiffer, Martin S. Tallman, Peter H. Wiernik

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

In each case of acute promyelocytic leukemia (APL) one of three PML- RARα mRNA types is produced, depending on the break/fusion site in the PML gene that is linked to a common RARα gene segment: a short (S)-form type, PML exon 3 RARα exon 3; a long (L)-form type, PML exon 6 RARα exon 3; or a variable (V)-form type, variably deleted PML exon 6 RARα exon 3. We evaluated whether PML-RARα mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and Leukemia Group B. Of 279 clinically eligible cases, 230 were molecularly evaluable, and of these, 111 were randomized to receive remission induction therapy with all-trans retinoic acid (ATRA) and 119 with conventional chemotherapy. Nine cases not excluded by central pathology review were PML- RARα negative, and notably, none of five of these cases treated with ATRA achieved complete remission (CR). Among 221 PML-RARα-positive cases, there were 82 S-form cases (37%), 121 L-form cases (55%), and 18 V-form cases (8%). Before any antileukemic therapy, the S-form type, compared with the L-form type, was associated with higher values for the white blood cell (WBC) count (median 2,500/μL v 1,600/μL; P = .009), the percentage of blood blasts plus promyelocytes (median 29% v 8.5%; P = .03), and the absolute blood blasts plus promyelocytes (884/μL v 126/μL; P = .019). Also, an increased percentage of S-form versus L-form cases had the M3 valiant phenotype, 24% v 12% (P = .036). There were no differences between S-form and L-form cases in either CR rate (79% v 69%; P = .14) or disease free survival distribution (multivariate analysis adjusting for the association of S-form type and higher WBC count; P = .40). We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RARα mRNA, per se, does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients.

Original languageEnglish (US)
Pages (from-to)1656-1663
Number of pages8
JournalBlood
Volume90
Issue number4
StatePublished - Aug 15 1997
Externally publishedYes

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L Forms
Acute Promyelocytic Leukemia
Exons
Blood
Fusion reactions
Messenger RNA
Leukocyte Count
Granulocyte Precursor Cells
Oncology
Tretinoin
Genes
Remission Induction
Chemotherapy
Pathology
Disease-Free Survival
Leukemia
Leukocytes
Therapeutics
Multivariate Analysis
Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Association of PML-RARα fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia : An intergroup molecular study. / Gallagher, Robert E.; Willman, Cheryl L.; Slack, James L; Andersen, Janet W.; Li, Yun Ping; Viswanatha, David; Bloomfield, Clara D.; Appelbaum, Frederick R.; Schiffer, Charles A.; Tallman, Martin S.; Wiernik, Peter H.

In: Blood, Vol. 90, No. 4, 15.08.1997, p. 1656-1663.

Research output: Contribution to journalArticle

Gallagher, RE, Willman, CL, Slack, JL, Andersen, JW, Li, YP, Viswanatha, D, Bloomfield, CD, Appelbaum, FR, Schiffer, CA, Tallman, MS & Wiernik, PH 1997, 'Association of PML-RARα fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: An intergroup molecular study', Blood, vol. 90, no. 4, pp. 1656-1663.
Gallagher, Robert E. ; Willman, Cheryl L. ; Slack, James L ; Andersen, Janet W. ; Li, Yun Ping ; Viswanatha, David ; Bloomfield, Clara D. ; Appelbaum, Frederick R. ; Schiffer, Charles A. ; Tallman, Martin S. ; Wiernik, Peter H. / Association of PML-RARα fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia : An intergroup molecular study. In: Blood. 1997 ; Vol. 90, No. 4. pp. 1656-1663.
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title = "Association of PML-RARα fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: An intergroup molecular study",
abstract = "In each case of acute promyelocytic leukemia (APL) one of three PML- RARα mRNA types is produced, depending on the break/fusion site in the PML gene that is linked to a common RARα gene segment: a short (S)-form type, PML exon 3 RARα exon 3; a long (L)-form type, PML exon 6 RARα exon 3; or a variable (V)-form type, variably deleted PML exon 6 RARα exon 3. We evaluated whether PML-RARα mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and Leukemia Group B. Of 279 clinically eligible cases, 230 were molecularly evaluable, and of these, 111 were randomized to receive remission induction therapy with all-trans retinoic acid (ATRA) and 119 with conventional chemotherapy. Nine cases not excluded by central pathology review were PML- RARα negative, and notably, none of five of these cases treated with ATRA achieved complete remission (CR). Among 221 PML-RARα-positive cases, there were 82 S-form cases (37{\%}), 121 L-form cases (55{\%}), and 18 V-form cases (8{\%}). Before any antileukemic therapy, the S-form type, compared with the L-form type, was associated with higher values for the white blood cell (WBC) count (median 2,500/μL v 1,600/μL; P = .009), the percentage of blood blasts plus promyelocytes (median 29{\%} v 8.5{\%}; P = .03), and the absolute blood blasts plus promyelocytes (884/μL v 126/μL; P = .019). Also, an increased percentage of S-form versus L-form cases had the M3 valiant phenotype, 24{\%} v 12{\%} (P = .036). There were no differences between S-form and L-form cases in either CR rate (79{\%} v 69{\%}; P = .14) or disease free survival distribution (multivariate analysis adjusting for the association of S-form type and higher WBC count; P = .40). We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RARα mRNA, per se, does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients.",
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T1 - Association of PML-RARα fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia

T2 - An intergroup molecular study

AU - Gallagher, Robert E.

AU - Willman, Cheryl L.

AU - Slack, James L

AU - Andersen, Janet W.

AU - Li, Yun Ping

AU - Viswanatha, David

AU - Bloomfield, Clara D.

AU - Appelbaum, Frederick R.

AU - Schiffer, Charles A.

AU - Tallman, Martin S.

AU - Wiernik, Peter H.

PY - 1997/8/15

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N2 - In each case of acute promyelocytic leukemia (APL) one of three PML- RARα mRNA types is produced, depending on the break/fusion site in the PML gene that is linked to a common RARα gene segment: a short (S)-form type, PML exon 3 RARα exon 3; a long (L)-form type, PML exon 6 RARα exon 3; or a variable (V)-form type, variably deleted PML exon 6 RARα exon 3. We evaluated whether PML-RARα mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and Leukemia Group B. Of 279 clinically eligible cases, 230 were molecularly evaluable, and of these, 111 were randomized to receive remission induction therapy with all-trans retinoic acid (ATRA) and 119 with conventional chemotherapy. Nine cases not excluded by central pathology review were PML- RARα negative, and notably, none of five of these cases treated with ATRA achieved complete remission (CR). Among 221 PML-RARα-positive cases, there were 82 S-form cases (37%), 121 L-form cases (55%), and 18 V-form cases (8%). Before any antileukemic therapy, the S-form type, compared with the L-form type, was associated with higher values for the white blood cell (WBC) count (median 2,500/μL v 1,600/μL; P = .009), the percentage of blood blasts plus promyelocytes (median 29% v 8.5%; P = .03), and the absolute blood blasts plus promyelocytes (884/μL v 126/μL; P = .019). Also, an increased percentage of S-form versus L-form cases had the M3 valiant phenotype, 24% v 12% (P = .036). There were no differences between S-form and L-form cases in either CR rate (79% v 69%; P = .14) or disease free survival distribution (multivariate analysis adjusting for the association of S-form type and higher WBC count; P = .40). We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RARα mRNA, per se, does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients.

AB - In each case of acute promyelocytic leukemia (APL) one of three PML- RARα mRNA types is produced, depending on the break/fusion site in the PML gene that is linked to a common RARα gene segment: a short (S)-form type, PML exon 3 RARα exon 3; a long (L)-form type, PML exon 6 RARα exon 3; or a variable (V)-form type, variably deleted PML exon 6 RARα exon 3. We evaluated whether PML-RARα mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and Leukemia Group B. Of 279 clinically eligible cases, 230 were molecularly evaluable, and of these, 111 were randomized to receive remission induction therapy with all-trans retinoic acid (ATRA) and 119 with conventional chemotherapy. Nine cases not excluded by central pathology review were PML- RARα negative, and notably, none of five of these cases treated with ATRA achieved complete remission (CR). Among 221 PML-RARα-positive cases, there were 82 S-form cases (37%), 121 L-form cases (55%), and 18 V-form cases (8%). Before any antileukemic therapy, the S-form type, compared with the L-form type, was associated with higher values for the white blood cell (WBC) count (median 2,500/μL v 1,600/μL; P = .009), the percentage of blood blasts plus promyelocytes (median 29% v 8.5%; P = .03), and the absolute blood blasts plus promyelocytes (884/μL v 126/μL; P = .019). Also, an increased percentage of S-form versus L-form cases had the M3 valiant phenotype, 24% v 12% (P = .036). There were no differences between S-form and L-form cases in either CR rate (79% v 69%; P = .14) or disease free survival distribution (multivariate analysis adjusting for the association of S-form type and higher WBC count; P = .40). We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RARα mRNA, per se, does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients.

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