Inactivation of p53 and deletion of ATM in B-CLL patients in relation to IgVH mutation

• Název česky: Inaktivace p53 a delece ATM u B-CLL pacientů ve vztahu s IgVH
• Autoři: TRBUŠEK Martin; MALČÍKOVÁ Jitka; ŠMARDOVÁ Jana; KUHROVÁ Viera; MENTZLOVÁ Dita; BUKOVSKÁ Soňa; KUGLÍK Petr; DOUBEK Michael; BRYCHTOVÁ Yvona; POSPÍŠILOVÁ Šárka; DVOŘÁKOVÁ Dana; VORLÍČEK Jiří; MAYER Jiří; SVITÁKOVÁ Miluše; LINKOVÁ Věra; ZAČAL Jiří; KUJÍČKOVÁ Jitka
• Rok publikování: 2006
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Leukemia
• Fakulta / Pracoviště MU: Lékařská fakulta
• Obor: Onkologie a hematologie
• Klíčová slova: B-CLL FASAY IgVH p53 ATM previous treatment
• Popis: 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.