Adipocytes contribute to multiple myeloma drug resistance in a BMI-dependent manner

<p>Multiple Myeloma (MM) is the second most common blood cancer in the United States, with an expected number of 34,920 new cases to be diagnosed this year (2020) (Key Statistics About Multiple Myeloma, 2021). Multiple myeloma arises from a specific white blood cell called a plasma cell. Plasma cells normally produce antibodies to fight infection, but MM plasma cells produce non-functional antibodies (Kyle & Rajkumar, 2009). This is problematic because MM cells crowd out functional red blood and white blood cells, leading to immune deficiencies and anemia (Kyle & Rajkumar, 2009). The cancerous plasma cells can also accumulate inside bones, causing bones to become frail. This explains how cancer gets its name; patients develop multiple tumors in the bone marrow (Ghobrial, 2012). Multiple myeloma is positively associated with obesity, which is increasing at an alarming rate in the U.S. (Basen-Engquist, & Chang, 2011). Obesity is known to increase cancer growth, inflammation, and drug resistance in many cancers (Pérez-Hernández et al., 2014; Pelicano, Carney, & Huang, 2004). The two mechanisms of drug resistance that are of focus are multidrug resistance (MDR) and cell adhesion mediated drug resistance (CAM-DR). RPMI 8226 and U266B multiple myeloma cell lines both exhibited increased drug resistance protein expressions when they were co-cultured with obese adipocytes compared to normal adipocytes. Interestingly, normal adipocytes seemed to induce CAM-DR protein production more than MDR protein, possibly indicating intrinsic resistance for normal adipocytes rather than acquired drug resistance.</p>