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Splenectomy: a new treatment option for ALL tumors expressing Hox-11 and a means to test the stem cell hypothesis of cancer in humans

Leukemia volume 21, pages 2192–2194 (2007)Cite this article

In the cancer field, rare stem cells are thought essential to the onset, perpetuation and recurrences of human cancers. To date, cancer stem cells have been identified as causal in some malignancies, such as acute myelogenous leukemia, chronic myelogenous leukemias, B-cell lymphoblastic leukemias and possibly solid tumors.1 The cancer stem cells based on this hypothesis are both necessary and sufficient for cancer growth and can be expanded in culture, unlike the cancer cells themselves. Therefore, an overriding goal in oncology has become the identification and eradication of the rare stem cells capable of sustained growth of the neoplasm—in lieu of the cancer itself. Ideally, those stem cells might be localizable in special reservoirs that would be targeted for therapeutics.

The strongest support for the cancer stem cell hypothesis has come from studies of acute myelogenous leukemia. A key study, for example, showed that only a small fraction of cells from human acute myelogenous leukemia, when transplanted into mice, managed to sustain tumor growth.2 This xenotransplant study was consistent with the clinical success of bone marrow (BM) transplants for acute myelogenous leukemia based on the rationale that a few hematopoietic cancer stem cells in the marrow are responsible for tumor growth. Therefore, BM transplantation would likely decrease the burden of cancer stem cells with the BM transplant. However, a provocative article by Kelly and co-workers (2007) challenges the cancer stem cell hypothesis.3 It questions the mouse xenotransplant study by arguing that few human cancer cells could survive transplantation into mice to promote tumor growth, not because of rare cancer stem cells, but because few human cancer cells could survive in the mouse milieu. A better murine test of the cancer stem cell hypothesis, according to the authors, would come from mouse to mouse transplants as opposed to xenotransplants (human cancer cells into mice). Indeed, when they undertook a study of mouse cancer cells of diverse lineages into mice, they found that diverse murine cancer cells survived the transplantation into another murine host and there induced growth of lymphoid and myeloid malignancies. The authors argued that the cancer stem cell hypothesis needed more rigorous testing in different models.

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References

  1. Dalerba P, Cho RW, Clarke MF . Cancer stem cells: models and concepts. Annu Rev Med 2007; 58: 267–284.

    Article  CAS  Google Scholar 

  2. Hope KJ, Jim L, Dick JE . Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 2004; 5: 738–743.

    Article  CAS  Google Scholar 

  3. Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A . Tumor growth need not be driven by rare cancer stem cells. Science 2007; 317: 337.

    Article  CAS  Google Scholar 

  4. Kodama S, Davis M, Faustman DL . Diabetes and stem cell researchers turn to the lowly spleen. Science SAGE 2005; 2005: pe2.

    Google Scholar 

  5. Raju K, Tang S, Dube ID, Kamel-Reid S, Bryce DM, Breitman ML . Characterization and developmental expression of Tlx-1, the murine homolog of HOX11. Mech Dev 1993; 44: 51–64.

    Article  CAS  Google Scholar 

  6. Dear TN, Colledge WH, Carlton MB, Lavenir I, Larson T, Smith AJ et al. The Hox11 gene is essential for cell survival during spleen development. Development 1995; 121: 2909–2915.

    CAS  Google Scholar 

  7. Watt PM, Hoffmann K, Greene WK, Brake RL, Ford J, Kees UR . Specific alternative HOX11 transcripts are expressed in paediatric neural tumours and T-cell acute lymphoblastic leukaemia. GENE 2003; 323: 89–99.

    Article  CAS  Google Scholar 

  8. Keller G, Wall C, Fong AZ, Hawley TS, Hawley RG . Overexpression of HOX11 leads to immortalization of embryonic precursors with both primitive and definitive hematopoeitic potential. Blood 1998; 92: 877–887.

    CAS  Google Scholar 

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Acknowledgements

The Iacocca Foundation sponsored the funding for this report. The donation and retrieval of human spleens was made possible through the resources of the Human Data Biological Interchange. Dr Francisco Dieguez was supported in party by the NIH Endocrine Training Grant No. DK007028.

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Authors and Affiliations

  1. Immunobiology Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    F J Dieguez-Acuna, M Davis & D L Faustman

  2. Cell Biology, Harvard Medical School, Boston, MA, USA

    S P Gygi

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  1. F J Dieguez-Acuna
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  2. S P Gygi
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  4. D L Faustman
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Correspondence to D L Faustman.

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Dieguez-Acuna, F., Gygi, S., Davis, M. et al. Splenectomy: a new treatment option for ALL tumors expressing Hox-11 and a means to test the stem cell hypothesis of cancer in humans. Leukemia 21, 2192–2194 (2007). https://doi.org/10.1038/sj.leu.2404927

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