Targeting the bone marrow microenvironment in hematologic malignancies

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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
StatePublished - Apr 2004
Externally publishedYes

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Hematologic Neoplasms
Bone Marrow
Drug Resistance
Pharmaceutical Preparations
Tumor Microenvironment
Extracellular Matrix
Leukemia
Cell Death
Phenotype
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Dalton, W. S., Hazlehurst, L., Shain, K., Landowski, T. H., & Alsina, M. (2004). Targeting the bone marrow microenvironment in hematologic malignancies. Seminars in Hematology, 41(2 SUPPL. 4), 1-5.

Targeting the bone marrow microenvironment in hematologic malignancies. / Dalton, William S.; Hazlehurst, Lori; Shain, Kenneth; Landowski, Terry H; Alsina, Melissa.

In: Seminars in Hematology, Vol. 41, No. 2 SUPPL. 4, 04.2004, p. 1-5.

Research output: Contribution to journalArticle

Dalton, WS, Hazlehurst, L, Shain, K, Landowski, TH & Alsina, M 2004, 'Targeting the bone marrow microenvironment in hematologic malignancies', Seminars in Hematology, vol. 41, no. 2 SUPPL. 4, pp. 1-5.
Dalton WS, Hazlehurst L, Shain K, Landowski TH, Alsina M. Targeting the bone marrow microenvironment in hematologic malignancies. Seminars in Hematology. 2004 Apr;41(2 SUPPL. 4):1-5.
Dalton, William S. ; Hazlehurst, Lori ; Shain, Kenneth ; Landowski, Terry H ; Alsina, Melissa. / Targeting the bone marrow microenvironment in hematologic malignancies. In: Seminars in Hematology. 2004 ; Vol. 41, No. 2 SUPPL. 4. pp. 1-5.
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