title: FISH+CD34+CD38- cells detected in newly diagnosed acute myeloid leukemia patients can predict the clinical outcome.
abstract: BACKGROUND
  In acute myeloid leukemia (AML), the leukemia initiating cells (LICs) or leukemia stem cells (LSCs) is found within the CD34+CD38- cell compartment. The LICs subpopulation survives chemotherapy and is most probable the cause of minimal residual disease (MRD), which in turn is thought to cause relapse. The aim of this study was to determine the prognostic value of the percentage of LICs in blasts at diagnosis.
  
  
  METHODS
  The percentage of LICs in the blast population was determined at diagnosis using a unique Flow-FISH analysis, which applies fluorescent in situ hybridization (FISH) analysis on flow cytometry sorted cells to distinguish LICs within the CD34+CD38- cell compartment. Fourty-five AML patients with FISH-detectable cytogenetic abnormalities treated with standardized treatment program were retrospectively included in the study. Correlations with overall survival (OS), events-free survival (EFS) and cumulative incidence of relapse (CIR) were evaluated with univariate and multivariate analysis.
  
  
  RESULTS
  The percentage of LICs is highly variable in patients with acute myeloid leukemia, ranged from 0.01% to 52.8% (median, 2.1%). High LIC load (≥1%) negatively affected overall survival (2-year OS: 72.57% vs. 16.75%; P = 0.0037) and events-free survival (2-year EFS: 67.23% vs. 16.33%; P = 0.0018), which was due to an increased cumulative incidence of relapse (2-year CIR: 56.7% vs. 18.0%; P = 0.021). By multivariate analysis, high LIC load retained prognostic significance for OS and EFS.
  
  
  CONCLUSIONS
  In the present study, we established the Flow-FISH protocol as a useful method to distinguish normal and leukemic cells within the CD34+CD38- cell subpopulation. The high percentage of LICs at diagnosis was significantly correlated with increased risk of poor clinical outcome.
authors: Libing
authors: L
authors: Wang
authors: Lei
authors: L
authors: Gao
authors: Sheng
authors: S
authors: Xu
authors: Shenglan
authors: S
authors: Gong
authors: Li
authors: L
authors: Chen
authors: Shuqing
authors: S
authors: Lü
authors: Jie
authors: J
authors: Chen
authors: Huiying
authors: H
authors: Qiu
authors: Xiaoqian
authors: X
authors: Xu
authors: Xiong
authors: X
authors: Ni
authors: Xianmin
authors: X
authors: Song
authors: Weiping
authors: W
authors: Zhang
authors: Jianmin
authors: J
authors: Yang
authors: Min
authors: M
authors: Liu
authors: Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. hu_xiaoxia@126.com.
authors: Xiaoxia
authors: X
authors: Hu
authors: Jianmin
authors: J
authors: Wang
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D051997:ADP-ribosyl Cyclase 1