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Stem Cells

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

Leukemia volume 22, pages 1207–1213 (2008)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by grants from Ministry of Education, Culture, Sports, Science and Technology of Japan (FI) and National Institutes of Health (LDS).

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Authors and Affiliations

  1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Y Kong, S Yoshida, M Fukata, N Saito, C Iwamoto & M Harada

  2. Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China

    Y Kong, S M Yang, K Y Liu, X J Huang & D P Lu

  3. Research Unit for Human Disease Models, RIKEN Research Center for Allergy and Immunology (RCAI), Yokohama, Japan

    Y Kong, S Yoshida, Y Saito, T Doi & F Ishikawa

  4. Department of Pediatrics, Kyushu National Cancer Center, Fukuoka, Japan

    Y Nagatoshi & J Okamura

  5. The Jackson Laboratory, Bar Harbor, Maine, USA

    L D Shultz

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  1. Y Kong
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  2. S Yoshida
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Correspondence to F Ishikawa.

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Kong, Y., Yoshida, S., Saito, Y. et al. CD34+CD38+CD19+ as well as CD34+CD38−CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL. Leukemia 22, 1207–1213 (2008). https://doi.org/10.1038/leu.2008.83

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