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

Yoshikane Kikushige, Fumihiko Ishikawa, Toshihiro Miyamoto, Takahiro Shima, Shingo Urata, Goichi Yoshimoto, Yasuo Mori, Tadafumi Iino, Takuji Yamauchi, Tetsuya Eto, Hiroaki Niiro, Hiromi Iwasaki, Katsuto Takenaka, Koichi Akashi

研究成果: Contribution to journalArticle査読

176 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)246-259
ページ数14
ジャーナルCancer Cell
20
2
DOI
出版ステータス出版済み - 8 16 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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