Targeting the bone marrow microenvironment in hematologic malignancies

William S. Dalton, Lori Hazlehurst, Kenneth Shain, Terry Landowski, Melissa Alsina

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Unicellular drug-resistant models have been critical in elucidating intrinsic drug-resistant mechanisms; however, these models do not consider resistance mechanisms that may be elicited by extrinsic influences such as the tumor microenvironment. We propose that specific niches within the tumor microenvironment may provide a sanctuary for subpopulations of tumor cells to evade or circumvent drug-induced death and that this may represent a form of de novo drug resistance. We have found that elements of the bone marrow microenvironment, including extracellular matrices and normal stromal elements, protect malignant cells, including leukemia and myeloma cells, from drug-induced cell death. This extrinsic form of drug resistance may allow cells to survive initial drug treatment and thereby acquire a more complex, intrinsic drug-resistant phenotype. Focusing on this form of do novo drug resistance may ultimately prevent the emergence of acquired drug resistance and enhance drug therapy for hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalSeminars in hematology
Volume41
Issue number2 SUPPL. 4
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Hematology

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