High frequency of p53 dysfunction and low level of V-H mutation in chronic lymphocytic leukemia patients using the V(H)3-21 gene segment

Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, England, United Kingdom
Blood (Impact Factor: 10.45). 09/2003; 102(3):1145-6. DOI: 10.1182/blood-2003-04-1289
Source: PubMed
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    • "A substantial proportion of patients expressing the IGHV3-21 gene are assigned to stereotyped Subset 2, the most populated CLL subset (Agathangelidis et al, 2012); this was reflected in our study, with 66/100 IGHV3-21 patients assigned to Subset 2. In line with the low number of TP53 defects in IGHV3-21 CLL, we observed a very low frequency also in Subset 2, similarly to a recent independent study (Rossi et al, 2013). Thus, both stereotyped and non-stereotyped IGHV3-21 CLL are associated with a relative paucity of TP53 defects, indicating that the high frequency of p53 pathway dysfunction observed within IGHV3-21 expressing CLL cases in a previous study (Lin et al, 2003) was probably due to causes other than TP53 defects. One possibility concerns defects in the ATM gene. "

    British Journal of Haematology 04/2014; 166(4). DOI:10.1111/bjh.12893 · 4.71 Impact Factor
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    • "Of interest , survival of M IGHV3 - 21 Scandinavian patients was worse than M CLL expressing non - IGHV3 - 21 genes , and was similar to survival of UM CLL ( Tobin et al , 2002 , 2003 ; Thorselius et al , 2006 ) . A comparably high frequency of IGHV3 - 21 gene usage ( about 9 – 10% ) has been detected also in British and Belgian CLL series ( Lin et al , 2003 ; Philippé et al , 2003 ; Matthews et al , 2004 ) . Conversely , in CLL series from Southern European countries ( i . "
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    ABSTRACT: The immunoglobulin heavy chain variable gene (IGHV) mutational status has been recognized as an important predictor of prognosis in chronic lymphocytic leukaemia (CLL) since 1999. More recently, other features of the B-cell receptor, such as stereotypy, have been identified as capable of refining the prognostic potential of IGHV status in the clinical assessment of CLL patients. In this context, different genes belonging to the IGHV3 subgroup, the most frequently used subgroup in CLL, have been shown to denote disease subsets that either display a bad prognosis (i.e. IGHV3-21, IGHV3-23) or are associated with particularly good clinical outcomes, including a highly stable/indolent clinical course, even prone to spontaneous regression (i.e. IGHV3-72, IGHV3-30). The present review focuses on the molecular and biological features of CLL-expressing specific genes belonging to the IGHV3 subgroup that are known to mark disease subsets with completely different clinical courses, and may be possibly related to CLL pathogenesis via antigen and/or superantigen involvement.
    British Journal of Haematology 02/2011; 153(1):3-14. DOI:10.1111/j.1365-2141.2010.08440.x · 4.71 Impact Factor
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    • "Vasconcelos Y, Davi F, Levy V, et al. Binet's staging system and VH genes are independent but complementary prognostic indicators in chronic lymphocytic leukemia. J Clin Oncol. 2003;21: 3928-3932. 35. Duke VM, Gandini D, Sherrington PD, et al. V(H) gene usage differs in germline and mutated B-cell chronic lymphocytic leukemia. Haematologica. 2003;88:1259-1271. 36. Messmer BT, Albesiano E, Messmer D, et al. The pattern and distribution of immunoglobulin VH gene mutations in chronic lymphocytic leukemia B cells are c"
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    ABSTRACT: We recently identified a chronic lymphocytic leukemia (CLL) subgroup using the immunoglobulin variable heavy-chain (V(H)) gene V(H)3-21 with almost identical heavy-chain complementarity determining region 3s (HCDR3s) and preferential variable light-chain (V(L)) gene usage, suggesting recognition of a common antigen epitope in this subset. To further explore the B-cell receptors (BCRs) in CLL, we characterized 407 V(H) rearrangements amplified from 346 CLLs regarding V(H), diversity (D), and joining (J(H)) gene usage and performed multiple alignment of the HCDR3 sequences. These analyses revealed 3 small subsets (2 V(H)1-69 groups, 7 cases; and 1 V(H)1-2 group, 5 cases) with highly restricted HCDR3 features including identical V(H)/D/J(H) usage, HCDR3 lengths, and shared N-sequences, in addition to the V(H)3-21 group (22 cases). Furthermore, another 3 groups (9 V(H)1-3(+) cases, 3 V(H)1-18(+) cases, and 5 V(H)4-39(+) cases) had essentially identical V(H)/D/J(H) use and similar HCDR3 lengths but less conserved N-regions. Analysis in all 6 of these subgroups showed restriction in V(L) gene use, whereas no association between V(H) and V(L) usage was found in cases without HCDR3 similarities. Altogether, structurally similar HCDR3s associated with preferential V(L) gene usage implies selection of BCRs, especially in subsets showing high HCDR3 similarities, thus pointing to restricted antigen recognition sites and possibly involvement of specific antigens in CLL development.
    Blood 12/2004; 104(9):2879-85. DOI:10.1182/blood-2004-01-0132 · 10.45 Impact Factor
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