title: Elevated TIM3+ hematopoietic stem cells in untreated myelodysplastic syndrome displayed aberrant differentiation, overproliferation and decreased apoptosis.
abstract: TIM3, as a negative regulator of anti-tumor immunity, is highly expressed on LSCs, but not on normal HSCs. TIM3 on HSCs in MDS patients has not been clarified. Here, both the percentage of TIM3 on HSCs and the MFI of TIM3+ HSCs were higher in untreated MDS than control and were closed to AML, and excessive TIM3+ HSCs was closely related to clinical parameters: WPSS score, karyotype analysis, morphologic blasts, the number of cytopenia involving hematopoietic lineages, anemia and granulocytopenia. TIM3+ HSCs expressed lower CD11b, TpoR, EpoR, G-CSFR and Annexin V, and higher CD71 and GATA2. TIM3+ HSCs displayed aberrant differentiation, overproliferation and decreased apoptosis. TIM3 might be a promising marker for identifying malignant clone cells in MDS and a candidate for targeted therapy.
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Jing-lian
authors.initials: JL
authors.lastname: Tao
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Li
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Hua-quan
authors.initials: HQ
authors.lastname: Wang
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Hui-juan
authors.initials: HJ
authors.lastname: Jiang
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Lan-zhu
authors.initials: LZ
authors.lastname: Yue
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Er-bao
authors.initials: EB
authors.lastname: Ruan
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Guo-jin
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Li-min
authors.initials: LM
authors.lastname: Xing
authors.affiliation: Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China. Electronic address: shaozonghong@sina.com.
authors.forename: Zong-hong
authors.initials: ZH
authors.lastname: Shao
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D050989:GATA2 Transcription Factor / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000473:pathology*; D011990:Receptors, Transferrin / Q000032:analysis
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D050989:GATA2 Transcription Factor; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D051997:ADP-ribosyl Cyclase 1
keywords: Apoptosis; Differentiation; Hematopoietic stem cells; Myelodysplastic syndrome; Proliferation; TIM3