Pathways to therapy resistance: The sheltering effect of the bone marrow microenvironment to multiple myeloma cells
Kuntal Bhowmick,
Max von Suskil,
Omar S. Al-Odat,
Weam Othman Elbezanti,
Subash C. Jonnalagadda,
Tulin Budak-Alpdogan,
Manoj K. Pandey
Affiliations
Kuntal Bhowmick
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
Max von Suskil
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
Omar S. Al-Odat
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
Weam Othman Elbezanti
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA; Department of Hematology, MD Anderson Cancer Center at Cooper, Cooper University Health Care, Camden, NJ, USA
Subash C. Jonnalagadda
Department of Chemistry and Biochemistry, College of Science and Mathematics, Rowan University, Glassboro, NJ, USA
Tulin Budak-Alpdogan
Department of Hematology, MD Anderson Cancer Center at Cooper, Cooper University Health Care, Camden, NJ, USA
Manoj K. Pandey
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA; Corresponding author. Department of Biomedical Sciences, Cooper Medical School of Rowan University, 401S Broadway, Camden, NJ, USA, 08103.
Multiple Myeloma (MM) is a malignant expansion of plasma cells in the bone marrow (BM), resulting in a disease characterized by symptoms of end organ damage from light chain secretion, crowding of the BM, and bone lesions. Although the past two decades have been characterized by numerous novel therapies emerging, the disease remains incurable due to intrinsic or acquired drug resistance. A major player in MM's drug resistance arises from its intimate relationship with the BM microenvironment (BMME). Through stress-inducing conditions, soluble messengers, and physical adhesion to BM elements, the BMME activates numerous pathways in the myeloma cell. This not only propagates myeloma progression through survival and growth signals, but also specific mechanisms to circumvent therapeutic actions. In this review, we provide an overview of the BMME, the role of individual components in MM survival, and various therapy-specific resistance mechanisms reported in the literature.
