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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
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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

Citace
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.

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