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Growth of human T cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID mouse fetal thymus organ culture

Leukemia volume 16, pages 1541–1548 (2002)Cite this article

Abstract

The in vitro proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells in its entirety has not been well delineated because of a lack of an appropriate culture system that mimics the growth pattern in a living body. We applied a NOD/SCID mouse fetal thymus organ culture (FTOC) for leukemic cells from fresh (one case) and frozen (seven cases) bone marrow (BM) samples of children with T-ALL. Cell growth was observed in all seven samples in the culture, reaching a proliferational peak at 4 weeks, and it was calculated that the proliferation potential was 212-to 319-fold. The FTOC-derived T-ALL cells showed similarity to the original cells morphologically and immunophenotypically, still possessed clonalities and were able to regenerate overt leukemia in NOD/SCID mice. These FTOC-derived T-ALL cells differed from ordinary cell lines because they always need FTOC support. Thus, we established a new in vitro culture for T-ALL cells. A comparison of the original and FTOC-derived T-ALL cells revealed that the proportion of cells expressing IL-7R increased in all seven cases. Sorting and re-seeding of FTOC-derived IL-7R+ and IL-7R− cells into secondary FTOC resulted in a predominant generation of IL-7R+ cells from both fractions, while IL-7R− cells proliferated more potently than did IL-7R+ cells, suggesting that a pathway for the conversion of IL-7R− to IL-7R+ exists during the proliferation of T-ALL lymphoblasts. Addition of exogenous IL-7 or neutralization with anti-IL-7 antibody did not influence the growth pattern of T-ALL cells in FTOC. The current study provides a unique assay system for the exploration of the hierarchy within human T-lymphoid leukemic cells, and should facilitate the establishment of novel therapeutic modalities.

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Authors and Affiliations

  1. Division of Cellular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    F Ma, A Manabe, D Wang, M Ito, M Wada & K Tsuji

  2. Division of Molecular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    S Asano

  3. Department of Bone Marrow Transplantation, Saitama Children's Medical Center, Saitama, Japan

    A Kikuchi

  4. Central Institute for Experimental Animals, Kawasaki, Japan

    M Ito

  5. Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan

    A Ohara

  6. St Luke's International Hospital, Tokyo, Japan

    R Hosoya

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  1. F Ma
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Ma, F., Manabe, A., Wang, D. et al. Growth of human T cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID mouse fetal thymus organ culture. Leukemia 16, 1541–1548 (2002). https://doi.org/10.1038/sj.leu.2402547

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  • DOI: https://doi.org/10.1038/sj.leu.2402547

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