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

Research output: Contribution to journalArticlepeer-review

183 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)246-259
Number of pages14
JournalCancer Cell
Volume20
Issue number2
DOIs
Publication statusPublished - Aug 16 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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