title: Expression of PML-RARα is up-regulated during ATRA and arsenics combined induction without influence on long-term prognosis of acute promyelocytic leukemia.
abstract: The early molecular kinetics during all-trans retinoic acid (ATRA) plus arsenic-based induction therapy and its prognostic value for acute promyelocytic leukemia (APL) remain unclear. This study was purposed to investigate the molecular and cytogenetic kinetics and its clinical significance in treatment of APL with ATRA plus arsenic-based induction. The molecular and cytogenetic kinetics was assessed by real-time quantitative RT-PCR and interphase fluorescence in situ hybridization (FISH) in 32 newly diagnosed APL patients. The results showed that the median PML-RARα transcript levels (PML-RARα/ABL) were very significantly up-regulated at 14 days of induction therapy compared with that of pre-treatment (40.10% vs 57.74%, P < 0.01), and then decreased at 28 days of induction therapy and at the end of consolidation therapy (6.97% and 0%), respectively. The total of 65.62% and 31.25% patients showed up-regulation of PML-RARα transcript at 14 and 28 days after induction, as compared with pretreatment. The PML-RARα copies per APL cell before treatment, and at 14 and 28 days after induction were calculated as 0.9, 2.2, 1.4 by the formula of PML-RARA/ABL(%)×2/APL cells (%). With the median follow-up time of 22 months, 32 patients were still in continuous clinical remission and no molecular relapse occurred. Up-regulation of PML-RARa expression during the induction had no effect on outcomes of APL patients. It is concluded that up-regulation of PML-RARa expression is a common event during induction therapy with ATRA plus arsenics. Up-regulation of PML-RARa expression during induction therapy hasn't influenced the long-term prognosis of APL.
authors.affiliation: Department of Hematology, Peking University People's Hospital; Peking University Institute of Hematology, Beijing 100044, China.
authors.forename: Hong-Hu
authors.initials: HH
authors.lastname: Zhu
authors.forename: Ya-Zhen
authors.initials: YZ
authors.lastname: Qin
authors.forename: Yue-Yun
authors.initials: YY
authors.lastname: Lai
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Shi
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001152:Arsenicals / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011379:Prognosis; D014212:Tretinoin / Q000008:administration & dosage; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: D001152:Arsenicals; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin