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/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.

Original languageEnglish
Pages (from-to)1207-1213
Number of pages7
JournalLeukemia
Volume22
Issue number6
DOIs
Publication statusPublished - Jun 2008

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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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