TY - JOUR
T1 - Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia
AU - Kikushige, Yoshikane
AU - Ishikawa, Fumihiko
AU - Miyamoto, Toshihiro
AU - Shima, Takahiro
AU - Urata, Shingo
AU - Yoshimoto, Goichi
AU - Mori, Yasuo
AU - Iino, Tadafumi
AU - Yamauchi, Takuji
AU - Eto, Tetsuya
AU - Niiro, Hiroaki
AU - Iwasaki, Hiromi
AU - Takenaka, Katsuto
AU - Akashi, Koichi
N1 - Funding Information:
We thank Drs. Jerome Ritz and Tetsuya Fukuda for helpful discussion. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology in Japan (to K.A. and T.M.) and a Grant-in-Aid from the Ministry of Health, Labour and Welfare in Japan (to K.A.).
PY - 2011/8/16
Y1 - 2011/8/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2011.06.029
DO - 10.1016/j.ccr.2011.06.029
M3 - Article
C2 - 21840488
AN - SCOPUS:80051589767
SN - 1535-6108
VL - 20
SP - 246
EP - 259
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -
