Frequent occurrence of highly expanded but unrelated B-cell clones in patients with multiple myeloma.

Clonal diversity in multiple myeloma (MM) includes both MM-related and MM-unrelated clonal expansions which are subject to dominance exerted by the MM clone. Here we show evidence for the existence of minor but highly expanded unrelated B-cell clones in patients with MM defined by their complementary determining region 3 (CDR3) peak. We further characterize these clones over the disease and subsequent treatment.

In multiple myeloma, bone-marrow lymphocytes harboring the same chromosomal abnormalities as autologous plasma cells predict poor survival.

Chromosomal abnormalities in plasma cells (PCs) from multiple myeloma (MM) provide a clonal signature to identify malignant cells. BM-lymphocytes from MM aspirates, defined by stringent criteria, were screened for the same chromosomal abnormalities as autologous PCs, including translocations, deletions, and amplifications. For 200 MM patients, we evaluated BM mononuclear cells to identify lymphocytes and autologous PCs on the same slide, followed by interphase fluorescence in situ hybridization to characterize their chromosomal abnormalities.

An integrated microfluidic chip for chromosome enumeration using fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) is a powerful technique for probing the genetic content of individual cells at the chromosomal scale. Conventional FISH techniques provide a sensitive diagnostic tool for the detection of chromosomal alterations on a cell-by-cell basis; however, the cost-per-test in terms of reagent and highly qualified labour has prevented its wide-spread utilization in clinical settings. Here, we address the inefficient use of labour with the first integrated and automated on-chip FISH implementation, one that requires only minutes of setup time from the technician.

The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma.

Aneuploid is ubiquitous in multiple myeloma (MM), and 4 cytogenetic subcategories are recognized: hypodiploid (associated with a shorter survival), pseudodiploid, hyperdiploid, and near-tetraploid MM. The hypodiploid, pseudodiploid, and near-tetraploid karyotypes can be referred to as the nonhyperdiploid MM. Immunoglobulin heavy-chain (IgH) translocations are seen in 60% of patients.