Abstract
Multiple myeloma is a clonal disease of long-lived plasma cells and is the second most common hematological cancer behind Non-Hodgkin’s Lymphoma. Malignant transformation of plasma cells imparts the ability to proliferate, causing harmful lesions in patients. In advanced stages myeloma cells become independent of their bone marrow microenvironment and form extramedullary disease. Plasma cells depend on a rich array of signals from neighboring cells within the bone marrow for survival which myeloma cells exploit for growth and proliferation. Recent evidence suggests, however, that both the myeloma cells and the microenvironment have undergone alterations as early as during precursor stages of the disease. There are no current therapies routinely used for treating myeloma in early stages, and while recent therapeutic efforts have improved patients’ median survival, most will eventually relapse. This is due to mutations in myeloma cells that not only allow them to utilize its bone marrow niche but also facilitate autocrine pro-survival signaling loops for further progression. This review will discuss the stages of myeloma cell progression and how myeloma cells progress within and outside of the bone marrow microenvironment.
Highlights
Recognizing the important role cytogenetics play in risk stratification, revised International Staging System (ISS) (R-ISS) was recently developed still utilizing the ISS, but incorporating both serum lactate dehydrogenase (LDH) levels as well as high risk cytogenetics defined by IgH-MMSET/FGFR3 [t(4,14)] translocations, IgH-MAF [t(14,16)] translocations, and deletion of the p arm of chromosome 17 (Table 1)
While myeloma cells can be seen circulating in peripheral blood in advanced stages, most Extramedullary multiple myeloma (EMM) is characterized by plasmacytomas in adjacent tissues and organs
Data that show microenvironment changes as early as MGUS propose that the microenvironment is susceptible to myeloma growth in precursor stages
Summary
Multiple myeloma (MM) is defined as a clonal proliferation of malignant plasma cells, and it accounts for roughly 10% of all hematological cancers [1]. There are ~70 patient-derived myeloma cell lines (HMCL), representing the most advanced stage of myeloma progression whereby myeloma cells survive independently of the bone marrow microenvironment. To this effect, myeloma cells can be compared to an expansive civilization that strategically taps the resources of its niche and when left unchecked will colonize and overtake its host. This review will examine progression of disease from asymptomatic precursor states to MM while shining a light on the changes myeloma cells induce in themselves and within the microenvironment to enable such. It will address the signals that allow myeloma to survive independently of the bone marrow microenvironment in their quest for further growth and expansion
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