Oncotarget

Research Papers:

Colony-forming unit cell (CFU-C) assays at diagnosis: CFU-G/M cluster predicts overall survival in myelodysplastic syndrome patients independently of IPSS-R

Bing Li, Jinqin Liu, Shiqiang Qu, Robert Peter Gale, Zhen Song, Ruixian Xing, Junxia Liu, Yansong Ren, Zefeng Xu, Tiejun Qin, Yue Zhang, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Wenyu Cai, Peihong Zhang, Gang Huang, Zhijian Xiao _

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Oncotarget. 2016; 7:68023-68032. https://doi.org/10.18632/oncotarget.12105

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Abstract

Bing Li1,2,*, Jinqin Liu2,*, Shiqiang Qu1,*, Robert Peter Gale3, Zhen Song4, Ruixian Xing1, Junxia Liu5, Yansong Ren5, Zefeng Xu1,2, Tiejun Qin1, Yue Zhang1,2, Liwei Fang1, Hongli Zhang1, Lijuan Pan1, Naibo Hu1, Wenyu Cai6, Peihong Zhang6, Gang Huang7 and Zhijian Xiao1,2

1 MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

2 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

3 Department of Medicine, Haematology Section, Division of Experimental Medicine, Imperial College, London, United Kingdom

4 Medical Service Division, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

5 Cell Culture Laboratory, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

6 Department of Pathology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

7 Divisions of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

* Bing Li, Jinqin Liu and Shiqiang Qu have contributed equally to this study

Correspondence to:

Zhijian Xiao, email:

Keywords: myelodysplastic syndromes; colony-forming unit cell; prognosis

Received: April 29, 2016 Accepted: August 25, 2016 Published: September 18, 2016

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.


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