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The bone marrow microenvironment has recently been suggested to influence HSC aging, but the underlying mechanisms remain largely unknown.
The bone marrow microenvironment has a key role in regulating haematopoiesis, but its molecular complexity and response to stress are incompletely understood.
A better understanding of the molecular basis of chemotherapy resistance and the molecular sequelae of conventional cytotoxic and novel agents on MM cells and the bone marrow microenvironment has afforded the opportunity to study novel, rationally designed combination therapies in the clinic.
Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored.
As recently demonstrated, the bone marrow microenvironment has a lower oxygen concentration than other tissues, and stem cells are localized within the hypoxic regions [20], thereby indicating that hypoxia may be crucial for the maintenance of stem cells.
The bone marrow microenvironment has a dominant role in upregulation of Pim-2 in MM.
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Advances in the understanding of biology of the disease and of the bone marrow microenvironment have translated into important therapeutic advances in the past decade (Palumbo and Anderson, 2011).
The same experiments were performed on B-CLL cells co-cultured with mesenchymal stromal cells (MSCs) from healthy donors, since MSCs of the bone marrow microenvironment have been reported to protect B-CLL cells from apoptosis induced by conventional chemotherapeutics.
Laboratory and preclinical studies have shown that intracellular regulatory proteins and functional interactions between MM cells and the bone-marrow microenvironment have a pivotal role in the growth, survival, drug resistance, and malignant progression of MM cells.
A major area of investigation is the human bone marrow microenvironment, which has an essential role in promoting growth, survival, and drug resistance in MM.
These agents target specific pathways within MM cells and the bone marrow microenvironment that have been identified and characterized through careful preclinical investigation.
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