Genome-wide microarray-based comparative genomic hybridization analysis of lymphoplasmacytic lymphomas reveals heterogeneous aberrations.

Lymphoplasmacytic lymphoma (LPL) is not a sharply delineated lymphoma entity, either morphologically, phenotypically, or clinically. The diagnosis is often made by excluding other small cell lymphomas with plasmacytic differentiation, thus a genetic diagnostic marker would be of great benefit. Conventional cytogenetic techniques have previously demonstrated a deletion of 6q in a proportion of cases, varying from 7 to 55%.

Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas.

Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.

Detailed assessment of copy number alterations revealing homozygous deletions in 1p and 13q in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is characterized by over-expression of cyclin Dl as a result of the characteristic t(11;14)(q13;q32). However, this translocation alone has proven not to be sufficient for lymphomagenesis, suggesting the involvement of additional alterations. We have characterized 35 cases of MCL by array comparative genomic hybridization with an average resolution of 0.

Immunoglobulin gene analysis of mature B-cell malignancies: reconsideration of cellular origin and potential antigen involvement in pathogenesis.

Mature B-cell malignancies stem from B cells transformed at various developmental stages, accounting for the wide range of heterogeneous features observed in the different disease entities. Analysis of the immunoglobulin (Ig) genes can facilitate the identification of the normal B-cell counterpart of lymphomas and leukemias, as Ig genes acquire somatic hypermutation in germinal centers during the immune response to antigen. Therefore, lymphomas that derive from a naïve, pregerminal center B cell lack somatic hypermutation in the clonal Ig gene, whereas germinal center-derived lymphomas, such as diffuse large B-cell lymphoma and follicular lymphoma, display somatic hypermutation of their Ig genes.

Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia derives from an extensively hypermutated B cell that lacks ongoing somatic hypermutation.

Lymphoplasmacytic lymphoma (LPL) is a rare lymphoma thought to originate from a B cell stimulated to differentiate to a plasma cell, and which is usually accompanied by clonal IgM secretion, defining the diagnosis of Waldenstrom's macroglobulinemia (WM). However, the immunoglobulin variable heavy chain (VH) gene usage and the somatic hypermutation status have not been widely investigated in LPL. LPL biopsies (CD19+/CD20+/CD22+/CD5-/CD10-/CD23-/kappa+) from 14 patients were included most of whom had a serum IgM component of variable magnitude (two cases with IgG).

Heterogeneous somatic hypermutation status confounds the cell of origin in hairy cell leukemia.

Hairy cell leukemia (HCL) is thought to arise from a post-germinal center (GC) B-cell, however the exact normal counterpart remains unclear. We performed VH gene analysis of 32 HCL cases, revealing somatically mutated VH genes (<98% homology) in 27 cases and unmutated VH genes in five cases, four of which displayed germline VH genes. Intraclonal heterogeneity was evident in the majority of eight mutated HCLs investigated, although at a lower level compared to GC-derived lymphomas.

Mantle cell lymphomas with clonal immunoglobulin V(H)3-21 gene rearrangements exhibit fewer genomic imbalances than mantle cell lymphomas utilizing other immunoglobulin V(H) genes.

A preferential use of one particular immunoglobulin variable heavy chain gene, V(H)3-21, has recently been reported in mantle cell lymphoma, where almost all of these V(H)3-21+ mantle cell lymphomas showed usage of the same light chain Vlambda gene (Vlambda3-19) and also had a tendency towards improved prognosis. These findings suggested that V(H)3-21+ mantle cell lymphomas constitute a distinct subgroup, possibly with antigen stimulation involved in disease pathogenesis. In this study, we applied the comparative genomic hybridization (CGH) method on 37 mantle cell lymphoma tumors in order to investigate if the V(H)3-21+ tumors are different at the genomic level.

Mutated VH genes and preferential VH3-21 use define new subsets of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of MCL displayed mutated V(H) genes. We also reported restricted use of certain V(H) genes.