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102 results on '"CD38 expression"'

101. Mutational status of IgVH genes consistent with antigen-driven selection but not percent of mutations has prognostic impact in B-cell chronic lymphocytic leukemia

Author

Carlo Pucillo, Alfonso Colombatti, E. Canton, Agostino Steffan, Massimo Degan, Riccardo Bomben, Valter Gattei, Maurizio Rupolo, Daniela Damiani, Pier Ferruccio Ballerini, Antonella Zucchetto, Vincenza Attadia, Massimiliano Berretta, Michele Dal Bo, Paola Nanni, and Anna Stefanon

Subjects
Adult, Male, Cancer Research, Time Factors, Chronic lymphocytic leukemia, DNA Mutational Analysis, Immunoglobulin Variable Region, V-H GENES, medicine.disease_cause, DISEASE, Germline mutation, Antigens, CD, CD38 EXPRESSION, CLL, medicine, Humans, Antigens, ADP-ribosyl Cyclase, Gene, Aged, Aged, 80 and over, Mutation, Membrane Glycoproteins, Genes, Immunoglobulin, biology, Germinal center, Cell Differentiation, Middle Aged, Prognosis, medicine.disease, ADP-ribosyl Cyclase 1, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Immunology, biology.protein, Cancer research, Female, Antibody
Abstract

Mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes, along with CD38 expression, is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL). Configuration of IgVH genes displaying > 2% mismatch has been shown to correlate with longer survivals. In a series of 64 B-CLLs, we failed to confirm the prognostic value of the IgVH gene mutational status by using the suggested cutoff. However, the IgVH mutational status maintained its prognostic value only when evidence of antigen-driven selection could be documented. This was accomplished by applying statistical methods aimed at evaluating a significant skewing of replacement mutations from framework to complementary determining regions, as it occurs during germinal center differentiation of B cells. These data caution against wide application of the 2% somatic mutation cutoff as a prognostic determinant without demonstration of antigen-driven selection.

102. Prognostic factors in the UK LRF CLL4 trial

Author

Alison Morilla, Sue Richards, Jenny A. Orchard, Vasantha Brito-Bapapulle, Giles Best, Rachel Wade, Daniel Catovsky, Estella Matutes, Zadie Davis, and David Oscier

Subjects
Univariate analysis, Immunology, Significant difference, Cell Biology, Hematology, Biology, Biochemistry, Molecular biology, Response to treatment, Vh genes, Fludarabine, Cd38 expression, Overall survival, medicine, Short survival, medicine.drug
Abstract

The CLL4 trial randomised 777 previously untreated patients between Chlorambucil (Chlor), Fludarabine (Fluda) and Fludarabine with Cyclophosphamide (FC). The median follow-up is 21 months. VH gene mutation status using a 98% cut off, CD38 expression using a 7% cut off, ZAP70 expression (Orchard et al Lancet 2004) and interphase FISH were measured on samples taken at randomisation. In an interim analysis 253/397 patients had unmutated VH genes. 32 patients utilised the VH3-21 gene, of whom 27 showed restricted HCDR3 usage. 343/535 were CD38 positive and 131/261 were ZAP70 positive. 10/24 VH 3-21 cases were ZAP 70 positive, of whom 7 were unmutated. There was no significant association between VH genes and age, sex or a positive DAT. There were significant correlations between VH gene mutations and CD38, ZAP70 and FISH results. | | CD38+ | ZAP 70+ | p53 loss | Del 11q | Del 6q21 | Del 13q | Trisomy 12 | |:------------------------------------------------ | --------- | --------- | -------- | -------- | -------- | --------- | ---------- | | % = % of all cases with known VH mutation status | | VH Unmutated | 119 (58%) | 110 (72%) | 21 (9%) | 48 (22%) | 18 (10%) | 109 (45%) | 50 (21%) | | VH Mutated | 30 (25%) | 17 (16%) | 3 (2%) | 13 (11%) | 6 (6%) | 97 (73%) | 13 (10%) | | p=

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