Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia

被引：232

作者：

Kikushige, Yoshikane ^{[1
]}

Ishikawa, Fumihiko ^{[2
]}

Miyamoto, Toshihiro

Shima, Takahiro ^{[1
]}

Urata, Shingo

Yoshimoto, Goichi

Mori, Yasuo

Iino, Tadafumi ^{[1
]}

Yamauchi, Takuji

Eto, Tetsuya ^{[3
]}

Niiro, Hiroaki

Iwasaki, Hiromi ^{[1
]}

Takenaka, Katsuto

Akashi, Koichi ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan

[2] RIKEN Ctr Allergy & Immunol, Res Unit Human Dis Model, Kanagawa 2300045, Japan

[3] Hamanomachi Hosp, Dept Hematol, Fukuoka 8108539, Japan

来源：

CANCER CELL | 2011年 / 20卷 / 02期

关键词：

ACUTE MYELOID-LEUKEMIA; B-CELLS; FOSTAMATINIB DISODIUM; ANTIGEN RECEPTORS; DENDRITIC CELLS; CORD BLOOD; T-CELLS; IMMUNOGLOBULIN; EXPRESSION; CHAIN;

D O I：

10.1016/j.ccr.2011.06.029

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We report here that in chronic lynnphocytic 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.

引用

页码：246 / 259

页数：14

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