title: Colony-forming unit cell (CFU-C) assays at diagnosis: CFU-G/M cluster predicts overall survival in myelodysplastic syndrome patients independently of IPSS-R.
abstract: In vitro colony-forming unit cell (CFU-C) assays are usually-used to detect the quantitative and qualitative features of haematopoietic stem cells (HSCs). We studies CFU-C assays in bone marrow samples from 365 consecutive subjects with newly-diagnosed myelodysplastic syndrome (MDS). Data were interrogated for associations with prognosis.
  
  
  
  CFU-C assays were performed according to the protocol of MethoCultTM H4435 Enriched. 365 consecutive newly-diagnosed, untreated subjects with MDS diagnosed from July, 2007 to April, 2014 were studied. All subjects were reclassified according to the 2008 WHO criteria. Subjects were observed for survival until July 31, 2015. Follow-up data were available for 289 (80%) subjects. Median follow-up of survivors was 22 months (range, 1-85) months. Erythroid and myeloid colonies were isolated from each subject with one cytogenetic abnormality such as del(5/5q), +8, del(7/7q) or del(20q). Cytogenetic abnormalities of each colony were analyzed by fluorescence in situ hybridization (FISH). SPSS 17.0 software was used to make statistical analysis.
  
  
  
  The numbers of burst-forming units-erythroid (BFU-E), colony forming unit-erythroid (CFU-E) and colony forming unit-granulocytes/macrophages (CFU-G/M) were significantly lower than normals. A high ratio of cluster- to CFU-G/M was associated with poor-risk cytogenetics. In multivariable analyses a cluster- to CFU-G/M ratio >0.6 was an independent risk-factor for OS after adjusting for IPSS-R (HR 3.339, [95%CI 1.434-7.778]; P = 0.005) in very high-risk cohort.
  
  
  
  These data suggest abnormalities of proliferation and differentiation of erythroid and myeloid precursor cells in vitro parallel the ineffective hematopoiesis typical of MDS and may be useful in predicting outcomes of persons with higher-risk MDS.
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.|State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Jinqin
authors.initials: J
authors.lastname: Liu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Medicine, Haematology Section, Division of Experimental Medicine, Imperial College, London, United Kingdom.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Medical Service Division, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Song
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Ruixian
authors.initials: R
authors.lastname: Xing
authors.affiliation: Cell Culture Laboratory, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cell Culture Laboratory, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Ren
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.|State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Qin
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.|State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Fang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pan
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Naibo
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Pathology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Pathology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Divisions of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.affiliation: MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.|State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism; D002648:Child; D002869:Chromosome Aberrations; D003114:Colony-Forming Units Assay / Q000379:methods*; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D005260:Female; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics; D023461:Myeloid Progenitor Cells / Q000378:metabolism*; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
keywords: colony-forming unit cell; myelodysplastic syndromes; prognosis