To investigate a potential pathogenic role of ATM in B-cell tumorigenesis, we performed mutation analysis of ATM in 29 malignant lymphomas of B-cell origin (B-CLL = 27; mantle cell lymphoma, [MCL] = 2).
A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas).
The MEC-1 and GRANTA-519 cells can be especially recommended for in vivo study of p53-mutated chronic lymphocytic leukemia and ATM-mutated mantle cell lymphoma, respectively.
Immunoglobulin heavy chain and major translocation cluster bcl-1 gene rearrangements were detected in all 29 (100%) and in 12 (41%) of 29 mantle cell lymphoma samples, respectively.
On a genetic level, many cases of mantle cell lymphomas have the t(11;14)(q13;q32) that causes overexpression of cyclin-D1, a protein that can be demonstrated by immunohistochemistry in many examples of mantle cell lymphoma and that can be exploited diagnostically to distinguish mantle cell lymphomas from other low-grade B cell lymphoproliferative disorders.
In both cases, immunohistochemistry (CD20+, CD5+, cyclin D1+, CD10-, and CD23-), and demonstration of clonal immunoglobulin heavy chain and bcl-1 gene rearrangements by PCR analysis confirmed the diagnosis of mantle cell lymphoma.
Mantle cell lymphoma is a B cell lymphoproliferative disorder cytogenetically characterized by the t(11;14)(q13;q32) which at molecular level involves the Bcl-1/PRAD-1 gene.
11q13 translocation has been described in mantle cell lymphoma in the form of t(11;14) (q13;q32), with rearrangement and over-expression of the cyclin D1 gene.
Translocation t(11;14)(q13;q32)CCND1-IGH is typically associated with mantle cell lymphoma or a subset of plasma cell myeloma and is exceedingly rare in myeloid neoplasm.
Although the observed break points in the BCL-1 locus are not tightly clustered, its rearrangement has been documented in 40-70% of cases of mantle cell lymphoma, whereas it only rarely occurs in other B cell lymphomas.
Translocations involving BCL1 at 11q13 are strongly associated with mantle cell lymphoma. other nonrandom aberrations, especially deletions and, less frequently, translocations, involving bands 11q21-923 have been identified by chromosome banding analysis.
Recent studies have shown the nuclear expression of sox11 in mantle cell lymphoma, which raises the question about its possible association with t(11;14)(q13;q32), the genetic hallmark of mantle cell lymphoma leading to the overexpression of cyclin D1.