CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL

Y. Kong, S. Yoshida, Y. Saito, T. Doi, Y. Nagatoshi, M. Fukata, N. Saito, S. M. Yang, C. Iwamoto, J. Okamura, K. Y. Liu, X. J. Huang, D. P. Lu, L. D. Shultz, M. Harada, F. Ishikawa

研究成果: ジャーナルへの寄稿学術誌査読

129 被引用数 (Scopus)

抄録

The presence of rare malignant stem cells supplying a hierarchy of malignant cells has recently been reported. In human acute myelogenous leukemia (AML), the leukemia stem cells (LSCs) have been phenotypically restricted within the CD34+CD38- fraction. To understand the origin of malignant cells in primary human B-precursor acute lymphocytic leukemia (B-ALL), we established a novel in vivo xenotransplantation model. Purified CD34+CD38+CD19+, CD34+CD38-CD19+ and CD34+CD38-CD19- bone marrow (BM) or peripheral blood (PB) cells from three pediatric B-ALL patients were intravenously injected into sublethally irradiated newborn NOD/SCID/IL2rγnull mice. We found that both CD34+CD38+CD19+ and CD34+CD38-CD19+ cells initiate B-ALL in primary recipients, whereas the recipients of CD34+CD38-CD10-CD19- cells showed normal human hematopoietic repopulation. The extent of leukemic infiltration into the spleen, liver and kidney was similar between the recipients transplanted with CD34+CD38+CD19+ cells and those transplanted with CD34+CD38-CD19+ cells. In each of the three cases studied, transplantation of CD34+CD38+CD19+ cells resulted in the development of B-ALL in secondary recipients, demonstrating self-renewal capacity. The identification of CD34+CD38+CD19+ self-renewing B-ALL cells proposes a hierarchy of leukemia-initiating cells (LICs) distinct from that of AML. Recapitulation of patient B-ALL in NOD/SCID/ IL2rγnull recipients provides a powerful tool for directly studying leukemogenesis and for developing therapeutic strategies.

本文言語英語
ページ(範囲)1207-1213
ページ数7
ジャーナルLeukemia
22
6
DOI
出版ステータス出版済み - 6月 2008

!!!All Science Journal Classification (ASJC) codes

  • 血液学
  • 腫瘍学
  • 癌研究

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