Editors' ChoiceMultiple Myeloma

You Can Run, But You Can’t Hide

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Science Translational Medicine  13 Jun 2012:
Vol. 4, Issue 138, pp. 138ec103
DOI: 10.1126/scitranslmed.3004424

Guerilla warfare is sometimes described as a deadly game of hide-and-seek—and hematopoietic cancer cells appear to use some of these tactics to evade chemotherapy. Normal hematopoietic stem cells are found in specialized microenvironments—niches—in the spongy bone marrow, where signals promote stem cell self-renewal and function. Blood-progenitor or lymphoid system–derived cancer cells are thought to find refuge in these microenvironments as well, where such malignant cells are protected from death and eventually become resistant to chemotherapy. Most studies of these processes have been done in mutant mice, which lack features of human physiology. Groen et al. now address this issue by reconstructing a human hematopoietic niche in mice.

To recreate these human microenvironments, the authors loaded calcium phosphate scaffolds with human mesenchymal stem cells—multipotent cells found in hematopoietic niches—and injected these particles under the skin of immunodeficient mice. Within 8 weeks, human osteoblasts had developed and deposited bone in the scaffolds, which had also become vascularized. Mice were then injected with either normal or malignant hematopoietic progenitor cells, which engrafted onto the subcutaneous bone particles. The normal cells differentiated into various blood cell types, whereas the malignant cells (multiple myeloma cells derived from patients) formed tumors in the humanized bone. The authors followed the growth dynamics and response to therapy of the tumor cells with a bioluminescent marker and special imaging techniques. These studies revealed that the tumor cells colonized only the human niches and not the mouse bone. Furthermore, responses to various treatments in the mice were equivalent to those in the corresponding patients.

The model sets an important precedent for understanding and predicting the responses of human hematopoietic-derived malignant cells to specific chemotherapy treatments, offering new hope for devising more effective, and perhaps personalized, interventions. Moreover, additional questions can now be addressed: How does the bone marrow microenvironment participate in the survival and expansion of primary or metastatic cells? What are the key mechanisms that characterize such interactions? What factors contribute to the increased resistance to chemotherapy within such an environment?

R. W. J. Groen et al., Reconstructing the human hematopoietic niche in immune deficient mice, opportunities for studying primary multiple myeloma. Blood, 31 May 2012 (10.1182/blood-2012-03-414920). [Abstract]

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