Publication details
Inactivation of p53 and deletion of ATM in B-CLL patients in relation to IgVH mutation
| Authors | |
|---|---|
| Year of publication | 2006 |
| Type | Article in Periodical |
| Magazine / Source | Leukemia |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | B-CLL FASAY IgVH p53 ATM previous treatment |
| Description | Defects in either of the two cooperating tumor suppressors, p53 or ATM, confer an inferior prognosis for B CLL patients. The abnormalities were reported to be associated with the unmutated IgVH subtype and may thus arise as a consequence of its more aggressive behaviour. However a recent report has also clearly correlated the p53 inactivation to a DNA damaging chemotherapy including alkylating agents (Sturm et al., Cell Death Differ 2003, 10: 477 to 484). We performed a comprehensive determination of p53 status in 168 B CLL samples (including functional FASAY analysis) and a deletion screening of ATM locus in 69% of the corresponding samples and correlated the data to the IgVH mutation status and to previous treatment. Inactivation of the p53 (overall frequency 12%) occurred markedly more frequently (P 0.05) and deletions of ATM (overall frequency 18%) strictly (P 0.001) in the unmutated IgVH subtype. A statistically significant correlation was not achieved between the presence of previous treatment (including alkylating agents in 44/49 cases) and the p53 or ATM abnormalities. In the IgVH unmutated subgroup, where the treatment was markedly more frequent, the proportion of the defects was similar in untreated/treated groups of patients. The p53/ATM inactivation does not seem to be primarily a consequence of DNA damaging chemotherapy. |