Light-chain only multiple myeloma is due to the absence of functional (productive) rearrangement of the IgH gene at the DNA level

Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains

“…This switching process usually occurs on one allele whilst in a large proportion of MM the other allele is involved in translocations with putative oncogenic partners; 4,5 however, both alleles of the IgH gene may be involved in such translocation events. [4][5][6] In IIGMM one allele is involved in a productive rearrangement of the V-D-J genes allowing the production of a functional heavy chain whereas in light-chain MM the IgH gene is either in germline configu- given as salvage therapy, 5) melphalan and prednisolone given as further salvage with little effect. It should be noted that light chains were not detected by protein electrophoresis and immunofixation electrophoresis on urine at diagnosis or throughout the course of the illness until the development of LEPP.…”

“…5,6 The most plausible explanation for the lack of heavy chain secretion seen in LEPP is the accumulation of genetic mutations during clonal evolution that compromise the production of intact heavy chains. Mechanisms including lack of IgH mRNA transcription, instability or degradation of IgH mRNA or translation errors could underlie this loss of capacity.…”

Tumors Escape CD4+ T-cell–Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens

“…40), which increases susceptibility to cell death by added stressors such as reactive oxygen species. Thus, the balance of L and H chain synthesis might represent a tradeoff between a need to avoid heavy chainmediated cytotoxicity (41) and beneficial effects of reduced L chain availability in the face of the Id-specific T-cell response. Whereas outgrowth of tumor cells secreting only L chains is observed in a subset of myeloma patients during disease progression (so-called "FLC escape"; refs.…”

Constipated myeloma

“…Careful clinicopathologic and cytogenetic analyses of individual cases by many investigators have defined distinctive subtypes of this disease. 1 Large epidemiologic surveys have defined high-risk patient populations. Patients with Hodgkin lymphoma were the first large cohort of cancer patients who experienced prolonged survival; hundreds of cases of therapy-related leukemia have now been reported within this group.…”

“…Recent analyses of LCMMs have shown that the tumors lack a functional IgH rearrangement, providing a molecular basis for this condition. 1 There has not been a comprehensive analysis of NSMMs, and previous reports have emphasized acquired mutations in the immunoglobulin light chain variable genes that lead to a block in secretion. [2][3][4] Thus from the information available there appears to be a fundamental difference in these 2 conditions, which otherwise share many features (eg, very high incidence of t(11;14)).…”