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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.
Kong, Y 1,2,3; Yoshida, S 1,3; Saito, Y 3; Doi, T 3; Nagatoshi, Y 4; Fukata, M 1; Saito, N 1; Yang, S M 2; Iwamoto, C 1; Okamura, J 4; Liu, K Y 2; Huang, X J 2; Lu, D P 2; Shultz, L D 5; Harada, M 1; Ishikawa, F 3
[Article] Leukemia. 22(6):1207-1213, June 2008.

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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/IL2r[gamma]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/IL2r[gamma]null recipients provides a powerful tool for directly studying leukemogenesis and for developing therapeutic strategies.