An update on molecular biology and drug resistance mechanisms of multiple myeloma

Abstract

Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromosomal abnormalities, oncogene activation and growth factor dysregulation. Chemotherapy is the most commonly used treatment strategy in MM. However, MM is a difficult disease to treat because of its marked resistance to chemotherapy. MM has been shown to be commonly multidrug resistance (MDR)-negative at diagnosis and associated with a high incidence of MDR expression at relapse. This review deals with the molecular aspects of MM, drug resistance mechanisms during treatment and also possible new applications for overcoming drug resistance. © 2015 Elsevier Ireland Ltd

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

“…First, translocations involving the immunoglobulin heavy chain gene (IgH) on chromosome 14q32 have been detected in up to 65% of patients [318,330]. The two most common translocations are t (11:14) and t(4:14), while t(14:16) is less frequent [332]. Second, several chromosomal deletions have been detected in myeloma cells; the single most important abnormality is del17p13, which is associated with shorter survival and an adverse prognosis [333].…”

Inhibition of HIF1α-Dependent Upregulation of Phospho-l-Plastin Resensitizes Multiple Myeloma Cells to Frontline Therapy

“…In fact, at diagnosis, the MM patient is “MDR-negative”, however, after several successive therapies, MM patients relapse due to MDR phenotype. This MDR is characterized, among others, by the overexpression of ABC transporter proteins, mainly Pgp, MultiDrug Resistance Protein 1 (MRP1), and Breast Cancer Resistance Protein (BCRP) [ 57 ]. The detection of Pgp or BCRP are linked to a low response to treatment [ 57 , 58 ].…”

“…This MDR is characterized, among others, by the overexpression of ABC transporter proteins, mainly Pgp, MultiDrug Resistance Protein 1 (MRP1), and Breast Cancer Resistance Protein (BCRP) [ 57 ]. The detection of Pgp or BCRP are linked to a low response to treatment [ 57 , 58 ]. Resistant clones, possibly derived from side populations (cancer stem cell), have been detected in RRMM patients which overexpress ABC transporter proteins [ 59 , 60 ].…”

“…Resistant clones, possibly derived from side populations (cancer stem cell), have been detected in RRMM patients which overexpress ABC transporter proteins [ 59 , 60 ]. Many agents used in MM treatment are substrates of the Pgp pump, such as PIs, like Btz, and also, carfilzomib [ 57 ]. Hence, we set up an MM resistant cell line by using doxorubicin, as this drug induces an overexpression of ABC transporter [ 61 ].…”

RNAi-based Gene Therapy for Blood Genetic Diseases

“…Like leukemia, chemotherapy is the most common treatment for MM right now. However, it is remarkably resistant to chemotherapy [34]. Molecular therapy became an alternative treatment, and the introduction of bortezomib has contributed to the improved survival of patients with MM.…”