title: Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia.
abstract: We report here that in chronic lymphocytic leukemia (CLL), the propensity to generate clonal B cells has been acquired already at the hematopoietic stem cell (HSC) stage. HSCs purified from patients with CLL displayed lymphoid-lineage gene priming and produced a high number of polyclonal B cell progenitors. Strikingly, their maturation into B cells was restricted always to mono- or oligo-clones with CLL-like phenotype in xenogeneic recipients. These B cell clones were independent of the original CLL clones because they had their own immunoglobulin VDJ genes. Furthermore, they used preferentially VH genes frequently used in human CLL, presumably reflecting the role of B cell receptor signaling in clonal selection. These data suggest that HSCs can be involved in leukemogenesis even in mature lymphoid tumors.
authors.affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Kikushige
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shima
authors.forename: Shingo
authors.initials: S
authors.lastname: Urata
authors.forename: Goichi
authors.initials: G
authors.lastname: Yoshimoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Iino
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niiro
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Katsuto
authors.initials: K
authors.lastname: Takenaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D019070:Cell Lineage; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D051379:Mice; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD