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

doi:10.1038/leu.2008.83

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

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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/IL2rγ^null 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/ IL2rγ^null recipients provides a powerful tool for directly studying leukemogenesis and for developing therapeutic strategies.

Original language	English
Pages (from-to)	1207-1213
Number of pages	7
Journal	Leukemia
Volume	22
Issue number	6
DOIs	https://doi.org/10.1038/leu.2008.83
Publication status	Published - Jun 2008

All Science Journal Classification (ASJC) codes

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/leu.2008.83

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Kong, Y., Yoshida, S., Saito, Y., Doi, T., Nagatoshi, Y., Fukata, M., Saito, N., Yang, S. M., Iwamoto, C., Okamura, J., Liu, K. Y., Huang, X. J., Lu, D. P., Shultz, L. D., Harada, M., & Ishikawa, F. (2008). 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(6), 1207-1213. https://doi.org/10.1038/leu.2008.83

Kong, Y, Yoshida, S, Saito, Y, Doi, T, Nagatoshi, Y, Fukata, M, Saito, N, Yang, SM, Iwamoto, C, Okamura, J, Liu, KY, Huang, XJ, Lu, DP, Shultz, LD, Harada, M & Ishikawa, F 2008, 'CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL', Leukemia, vol. 22, no. 6, pp. 1207-1213. https://doi.org/10.1038/leu.2008.83

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

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.",

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

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

year = "2008",

month = jun,

doi = "10.1038/leu.2008.83",

language = "English",

volume = "22",

pages = "1207--1213",

journal = "Leukemia",

issn = "0887-6924",

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T1 - CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL

AU - Kong, Y.

AU - Yoshida, S.

AU - Saito, Y.

AU - Doi, T.

AU - Nagatoshi, Y.

AU - Fukata, M.

AU - Saito, N.

AU - Yang, S. M.

AU - Iwamoto, C.

AU - Okamura, J.

AU - Liu, K. Y.

AU - Huang, X. J.

AU - Lu, D. P.

AU - Shultz, L. D.

AU - Harada, M.

AU - Ishikawa, F.

N1 - Funding Information: This work was supported by grants from Ministry of Education, Culture, Sports, Science and Technology of Japan (FI) and National Institutes of Health (LDS).

PY - 2008/6

Y1 - 2008/6

N2 - 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.

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

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