title: Low WT1 transcript levels at diagnosis predicted poor outcomes of acute myeloid leukemia patients with t(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy. This study aimed to evaluate the impact of Wilm tumor gene-1 (WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase (C-KIT) mutations at diagnosis, and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.
  
  
  METHODS
  Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation (allo-HSCT) were included. Patients who achieved remission, received two or more cycles of consolidation chemotherapy, and had a positive measureable residual disease (MRD) test result (defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT. Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles. WT1 transcript levels and C-KIT mutations at diagnosis, and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.
  
  
  RESULTS
  Patients who had a C-KIT mutation had significantly lower WT1 transcript levels than patients who did not have a C-KIT mutation (6.7% ± 10.6% vs. 19.5% ± 19.9%, P < 0.001). Low WT1 transcript levels (≤5.0%) but not C-KIT mutation at diagnosis, a positive MRD test result after the second cycle of consolidation chemotherapy, and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients (hazard ratio [HR] = 3.53, 2.30, and 11.49; 95% confidence interval [CI] 1.64-7.62, 1.82-7.56, and 4.43-29.82; P = 0.002, 0.034, and <0.001, respectively); these conditions were also independently associated with low leukemia-free survival (HR = 3.71, 2.33, and 5.85; 95% CI 1.82-7.56, 1.17-4.64, and 2.75-12.44; P < 0.001, 0.016, and <0.001, respectively) and overall survival (HR = 3.50, 2.32, and 4.34; 95% CI 1.56-7.82, 1.09-4.97, and 1.98-9.53; P = 0.002, 0.030, and <0.001, respectively) in all patients.
  
  
  CONCLUSIONS
  Testing for WT1 transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission. A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Ya-Zhen
authors.initials: YZ
authors.lastname: Qin
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Hong-Hu
authors.initials: HH
authors.lastname: Zhu
authors.affiliation: Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Biostatistics Division, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
authors.forename: Mei-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Yue-Yun
authors.initials: YY
authors.lastname: Lai
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Beijing, P. R. China. xjhrm@medmail.com.cn.|Peking-Tsinghua Center for Life Sciences, Beijing, 100871, P. R. China. xjhrm@medmail.com.cn.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D060830:Consolidation Chemotherapy; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D000075142:RUNX1 Translocation Partner 1 Protein; D016019:Survival Analysis; D014178:Translocation, Genetic; D014184:Transplantation, Homologous; D025721:WT1 Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; D000970:Antineoplastic Agents; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; C-KIT mutation; RUNX1-RUNX1T1 transcript level; WT1 transcript level