Understanding biology to tackle the disease: Multiple myeloma from bench to bedside, and back

Abstract

Multiple myeloma (MM) is a cancer of antibody-producing plasma cells. The pathognomonic laboratory finding is a monoclonal immunoglobulin or free light chain in the serum and/or urine in association with bone marrow infiltration by malignant plasma cells. MM develops from a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage termed smoldering multiple myeloma (SMM), which differs from active myeloma by the absence of disease-related end-organ damage. Unlike MGUS and SMM, active MM requires therapy. Over the past 6 decades, major advancements in the care of MM patients have occurred, in particular, the introduction of novel agents (ie, proteasome inhibitors, immunomodulatory agents) and the implementation of hematopoietic stem cell transplantation in suitable candidates. The effectiveness and good tolerability of novel agents allowed for their combined use in induction, consolidation, and maintenance therapy, resulting in deeper and more sustained clinical response and extended progression-free and overall survival. Previously a rapidly lethal cancer with few therapeutic options, MM is the hematologic cancer with the most novel US Food and Drug Administration-approved drugs in the past 15 years. These advances have resulted in more frequent long-term remissions, transforming MM into a chronic illness for many patients.

Comprehensive profiling of circular RNA expressions reveals potential diagnostic and prognostic biomarkers in multiple myeloma

“…Multiple myeloma (MM) is the second most common hematological malignancy derived from long-lived antibodyproducing plasma cells in the bone marrow and is characterized by the presence of monoclonal immunoglobins in the serum and/or urine [1]. Over the past half century, the introduction of novel drugs (such as bortezomib) and application of hematopoietic stem cell transplantation have turned the rapid lethal MM into a chronic and manageable disease with extended survival in most of the patients [2,3]. However, MM lacks symptoms in early stage, and the identification of the disease onset is difficult to be achieved by current examinations [4].…”

Therapeutic Targeting of miR-29b/HDAC4 Epigenetic Loop in Multiple Myeloma

“…Multiple myeloma is a plasma cell malignancy characterized by a high genetic complexity and molecular heterogeneity (1). A number of epigenetic modifications have been so far linked to cancer, including posttranslational modification of histones, DNA methylation, and the most recently discovered noncoding RNAs, which are currently considered key determinants in human cancer pathogenesis (2).…”

Hyaluronan and proteoglycan link protein 1 (HAPLN1) activates bortezomib-resistant NF-κB activity and increases drug resistance in multiple myeloma

“…Multiple myeloma (MM) 4 is the second most common hematologic malignancy with over 30,000 new cases diagnosed annually in the United States. Currently, MM is generally considered an incurable disease with a median survival of 5-7 years from diagnosis (1). MM is characterized by the uncontrolled proliferation and accumulation of antibody-secreting plasma cells primarily in the bone marrow (1).…”