Association of PML-RARα Fusion mRNA Type With Pretreatment Hematologic Characteristics But Not Treatment Outcome in Acute Promyelocytic Leukemia: An Intergroup Molecular Study

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