title: Establishment of xenotransplantation model of human CN-AML with FLT3-ITD (mut) /NPM1 (-) in NOD/SCID mice.
abstract: Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tong-Juan
authors.initials: TJ
authors.lastname: Li
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. wangna.2001@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology* / Q000601:surgery; D008297:Male; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D014183:Transplantation, Heterologous / Q000379:methods*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3