title: Concordance of two approaches in monitoring of minimal residual disease in B-precursor acute lymphoblastic leukemia: Fusion transcripts and leukemia-associated immunophenotypes.
abstract: OBJECTIVE
  Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear.
  
  
  METHODS
  Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry.
  
  
  RESULTS
  MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively.
  
  
  CONCLUSIONS
  In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors.forename: Ying-Jung
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, National University of Singapore, Singapore.
authors.forename: Elaine
authors.initials: E
authors.lastname: Coustan-Smith
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Kao
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
authors.forename: Hsi-Che
authors.initials: HC
authors.lastname: Liu
authors.affiliation: College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Hematology-Oncology, Chang Gung Children's Hospital at Linkou, Toayuan, Taiwan.
authors.forename: Shih-Hsiang
authors.initials: SH
authors.lastname: Chen
authors.affiliation: College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Hsiao
authors.affiliation: Department of Hematology-Oncology, Chang Gung Children's Hospital at Linkou, Toayuan, Taiwan.
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Yang
authors.affiliation: College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Hematology-Oncology, Chang Gung Children's Hospital at Linkou, Toayuan, Taiwan.
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
authors.forename: Ting-Chi
authors.initials: TC
authors.lastname: Yeh
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Kuo
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors.forename: Chang-Liang
authors.initials: CL
authors.lastname: Lai
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, National University of Singapore, Singapore.
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. Electronic address: dcliang@mmh.org.tw.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Liang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: sly7012@adm.cgmh.org.tw.
authors.forename: Lee-Yung
authors.initials: LY
authors.lastname: Shih
mesh_terms: D000208:Acute Disease; D001853:Bone Marrow / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D018365:Neoplasm, Residual / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D015514:Oncogene Proteins, Fusion; C543638:TCF3-PBX1 fusion protein, human
keywords: B-precursor acute lymphoblastic leukemia; flow cytometry; fusion transcripts; minimal residual disease