multiple myeloma, Waldenström macroglobulinemia, or other B cell-associated neoplasm, that has developed, often in a stepwise manner, from their MGUS precursors.The clinical importance of understanding this spectrum of diseases is that it can be used to: a) advise individuals on the likelihood of their condition progressing to a malignant phase; b) monitor individuals for the many complications that may occur at any stage of the dyscrasias so that they can be treated to avoid or reduce their clinical impacts; and c) monitor patients for transitions to malignancy so that the malignancy can be treated at an early stage when treatment results are best. Unless otherwise noted, the advice and monitoring given here are those recommended by the International Myeloma Working Group in 2014 and updated in 2016. Clonal plasma cells
Plasma cells are key effector elements of the adaptive immune system. They contribute to immunity by making antibodies that bind with and thereby initiate the process of neutralizing specific antigens that usually are found on the surface of invading pathogens and foreign substances. Plasma cells develop from B lymphocytes (i.e. B cells) which are stimulated to undergo this maturational development by T lymphocytes during the latter cells processing of these antigens. As they are stimulated to become plasma cells, B cells refashion parts of their genome in efforts to create a new gene that encodes a functional antibody.
In humans, antibodies are composed of two identical heavy chains which are of the gamma (γ), alpha (α), epsilon (ε), delta (δ), or mu (μ) subtypes and two identical light chains which are of the kappa (κ) or lambda (λ) subtypes. Antibodies are classified as IgG, IgA, IgE, IgD, and IgM based on their being made up of γ, α, ε, δ, or μ heavy chains, respectively. Formation of the genes that make these antibodies requires B cells and/or their descendent plasma cells to mutate, break, and recombine various genes at the immunoglobulin heavy chain antigen-binding locus on the long (i.e. "q") arm of human chromosome 14 at position 32.33 (notated as 14q32.33) and the immunoglobulin light chain antigen binding locus on the q arm of chromosome 22 at position 11.2 (i.e. 22 q11.2) by processes termed V(D)J recombination, somatic hypermutation, and immunoglobulin class switching. These genomic changes can go awry by placing a gene that controls cell growth an/or survival adjacent to a normally highly active antibody gene promoter and/or by causing the formation of extra chromosomes (see trisomy) or chromosomes with large deletions that result in the overexpression or under-expression, respectively, of genes that control cell growth and/or survival.