ATM mutations uniformly lead to ATM dysfunction in chronic lymphocytic leukemia: application of functional test using doxorubicin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F13%3A%230002201" target="_blank" >RIV/65269705:_____/13:#0002201 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/13:00065621

Result on the web

<a href="http://dx.doi.org/10.3324/haematol.2012.081620" target="_blank" >http://dx.doi.org/10.3324/haematol.2012.081620</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3324/haematol.2012.081620" target="_blank" >10.3324/haematol.2012.081620</a>

Result language

angličtina

Original language name

ATM mutations uniformly lead to ATM dysfunction in chronic lymphocytic leukemia: application of functional test using doxorubicin

Original language description

ATM abnormalities are frequent in chronic lymphocytic leukemia and represent an important prognostic factor. Sole 11q deletion does not result in ATM inactivation by contrast to biallelic defects involving mutations. Therefore, the analysis of ATM mutations and their functional impact is crucial. In this study, we analyzed ATM mutations in predominantly high-risk patients using: i) resequencing microarray and direct sequencing; ii) Western blot for total ATM level; iii) functional test based on p21 geneinduction after parallel treatment of leukemic cells with fludarabine and doxorubicin. ATM dysfunction leads to impaired p21 induction after doxorubicin exposure. We detected ATM mutation in 16% (22 of 140) of patients, and all mutated samples manifested demonstrable ATM defect (impaired p21 upregulation after doxorubicin and/or null protein level). Loss of ATM function in mutated samples was also evidenced through defective p53 pathway activation after ionizing radiation exposure. ATM

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2013

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Haematologica

ISSN

0390-6078

e-ISSN

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Volume of the periodical

98

Issue of the periodical within the volume

7

Country of publishing house

IT - ITALY

Number of pages

8

Pages from-to

1124-1131

UT code for WoS article

000328540200027

EID of the result in the Scopus database

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