Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphoma: analysis with multiple breakpoint probes

Abstract

Centrocytic lymphoma is a B-cell non-Hodgkin's lymphoma (NHL) composed of lymphocytes resembling cleaved follicular center cells (centrocytes). Previous studies have suggested an association between t(11;14) chromosomal translocations and bcl-1 rearrangement in centrocytic and related intermediate lymphocytic lymphomas. To further characterize the association between bcl-1 and centrocytic lymphoma, Southern blot analysis was performed on samples from 23 patients using four separate bcl-1 breakpoint probes spanning 63 kb of the chromosome 11 bcl-1 locus. Rearrangements were identified in six patients with the major translocation cluster (MTC) probe and in another six with probe p94PS, located about 24 kb 5′ of MTC. Eleven of these 12 cases showed comigration of rearranged bcl-1 and Ig heavy chain-joining genes, consistent with the t(11;14) chromosomal translocation. No rearrangements were observed with the bcl-1 locus probes p210 or p11EH located 5′ of p94PS, nor with bcl-2 or c-myc oncogene probes. No bcl-1 rearrangements were identified in B-cell follicular NHL (15), small noncleaved cell (Burkitt's and non-Burkitt's) NHL (8), T-cell NHL (4), multiple myeloma (14), and pre-B-cell acute lymphoblastic leukemia (9). One of 23 B-cell NHL of large cell type and one of 19 chronic lymphocytic leukemias or small lymphocytic NHL had MTC rearrangement. Thus, bcl-1 rearrangement occurred at MTC or p94PS in 12 of 23 centrocytic lymphomas (52%), confirming a nonrandom association and suggesting a pathogenetic role for the bcl-1 locus in this immunohistologic subtype of NHL.

In leukaemic CD5+ B cells the expression of BCL‐2 gene family is shifted toward protection from apoptosis

“…Interestingly, the anti-apoptotic pattern expression of Bcl-2 gene family observed in B-CLL cells is also shared by MCL cells. A major difference between MCL and CLL cells is the MCL over-expression of Bcl-1 (Williams et al, 1990(Williams et al, , 1991Medeiros et al, 1990;Bosch et al, 1994) that encodes the PRAD-1/cyclin D1 protein (Motokura et al, 1991;Xiong et al, 1991). Both B-CLL and MCL may present as CD5 B-cell chronic lymphoid leukaemias; however, the course and prognosis of the two entities are significantly different (Harris et al, 1994 III + + + + 28 MCL IV + ---29 MCL IV +/-+ + + 30 MCL IV + + + -31 MCL O + + --32 MCL II + + + -33 MCL IV +/ unreasonable to suggest that the pattern of expression of apoptosis/cell-cycle-related gene products may explain the different clinical behaviour of B-CLL v MCL.…”

“…Further, both entities show germline encoded VH region immunoglobulin (Ig) genes that reflect the absence of the germinal centre (GC)-based process of V region gene hypermutation (Hummel et al, 1994) and, together with phenotypic features (Kipps & Duffy, 1991), suggest their origination from a common pool of CD5 pre-GC B cells related to follicular mantle B cells (Harris et al, 1994;Caligaris-Cappio et al, 1993;Hummel et al, 1994). A distinctive feature of MCL is the rearrangement of Bcl-1, the molecular counterpart of the t(11;14) translocation (Williams et al, 1990(Williams et al, , 1991Medeiros et al, 1990), which causes the over-expression of the PRAD-1/Cyclin D1 protein (Bosch et al, 1994;Jadayel et al, 1994) involved in the control of cell cycle at the G1-S transition (Motokura et al, 1991;Xiong et al, 1991). Bcl-1 rearrangement and over-expression are, on the contrary, very rare in B-CLL cells (Rechavi et al, 1989;Raghobier et al, 1991;Newman et al, 1993;Bosch et al, 1994).…”

Blastoid and common variants of mantle cell lymphoma exhibit distinct immunophenotypic and interphase FISH features

“…1 The chromosomal translocation t(11;14)(q13;q32) results in the rearrangement and overexpression of the PRAD1 ⁄ cyclin D1 gene and is highly characteristic of MCL. [2][3][4][5][6][7][8] According to the World Health Organization (WHO) lymphoma classification, different MCL variants have been identified. However, only the blastic or blastoid variants (BV-MCL) are considered to be of potential clinical significance as they have a more aggressive course.…”

Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects

“…One of the major genetic hallmarks of MCL is the t(11:14) (q13:q32) chromosomal translocation between the cyclin D1 gene (CCND1) located on chromosome 11 and the immunoglobulin heavy-chain locus (IGH) on chromosome 14. This translocation leads to increased CCND1 transcription and CCND1 protein expression (Raffeld & Jaffe, 1991;Williams et al, 1991). CCND1 activates cyclin-dependent kinase (CDK) 4 and CDK6 that phosphorylate retinoblastoma protein (RB1), thereby activating the E2F transcription factor and leading to G1-S cell cycle progression (Sherr, LYN, LYN proto-oncogene, Src family tyrosine kinase;MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; MAP3K14, mitogen-activated protein kinase kinase kinase 14 (also termed NIK); MYD88, Myeloid differentiation primary response 88; NFKB, Nuclear factor kappa B; NFKB2, Nuclear factor kappa B subunit 2; PI3K, phosphatidylinositol-3-kinase; PRKCB, protein kinase Cb; RB1, retinoblastoma 1; RELA, RELA proto-oncogene, NF-kB subunit; RELB, RELB proto-oncogene, NF-kB subunitSYK, spleen tyrosine kinase; TLR, toll-like receptor; TRAF, tumour necrosis factor receptor-associated factor.…”