title: Targeting High Dynamin-2 (DNM2) Expression by Restoring Ikaros Function in Acute Lymphoblastic Leukemia.
abstract: Dynamin-2 (DNM2) is a GTPase essential for intracellular vesicle formation and trafficking, cytokinesis and receptor endocytosis. Mutations in DNM2 are common in early T-cell precursor acute lymphoblastic leukemia. However, DNM2 expression in other types of ALL are not reported. We studied DNM2 mRNA level in adults with B- and T-cell ALL. We found DNM2 is more highly expressed compared with normals in both forms of ALL. High DNM2 expression is associated with some clinical and laboratory features, inferior outcomes and with leukaemia cell proliferation. We also found Ikaros directly binds the DNM2 promoter and suppresses DNM2 expression. Consequently IKZF1 deletion is associated with high DNM2 expression. Conversely, casein kinase-2 (CK2)-inhibitor increases Ikaros function thereby inhibiting DNM2 expression. Inhibiting DNM2 suppresses proliferation of leukemia cells and synergizes with CK2 inhibition. Our data indicate high DNM2 expression is associated with Ikaros dysregulation and may be important in the development of B-ALL.
authors.affiliation: Department of Hematology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Hematology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hematology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
authors.affiliation: Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Pennsylvania State University Medical College, Hershey, PA 17033, USA.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Dovat
authors.affiliation: Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Department of Pediatrics, Pennsylvania State University Medical College, Hershey, PA 17033, USA.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Song
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D047390:Casein Kinase II / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D034285:Dynamin II; D034281:Dynamins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor; D047390:Casein Kinase II; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins