@article{Anna Guarini_Marilisa Marinelli_Simona Tavolaro_Emanuele Bellacchio_Monia Magliozzi_Sabina Chiaretti_Maria Stefania De Propris_Nadia Peragine_Simona Santangelo_Francesca Paoloni_Mauro Nanni_Ilaria Del Giudice_Francesca Romana Mauro_Isabella Torrente_Robin Foà_2011, place={Pavia, Italy}, title={ATM gene alterations in chronic lymphocytic leukemia patients induce a distinct gene expression profile and predict disease progression}, volume={97}, url={https://haematologica.org/article/view/6188}, DOI={10.3324/haematol.2011.049270}, abstractNote={<strong>Background</strong> The genetic characterization of chronic lymphocytic leukemia cells correlates with the behavior, progression and response to treatment of the disease.<strong>Design and Methods</strong> Our aim was to investigate the role of <em>ATM</em> gene alterations, their biological consequences and their value in predicting disease progression. The <em>ATM</em> gene was analyzed by denaturing high performance liquid chromatography and multiplex ligation probe amplification in a series of patients at diagnosis. The results were correlated with immunoglobulin gene mutations, cytogenetic abnormalities, ZAP-70 and CD38 expression, <em>TP53</em> mutations, gene expression profile and treatment-free interval.<strong>Results</strong> Mutational screening of the <em>ATM</em> gene identified point mutations in 8/57 cases (14%). Multiplex ligation probe amplification analysis identified six patients with 11q deletion: all of them had at least 20% of deleted cells, analyzed by fluorescent <em>in situ</em> hybridization. Overall, <em>ATM</em> point mutations and deletions were detected in 14/57 (24.6%) cases at presentation, representing the most common unfavorable genetic anomalies in chronic lymphocytic leukemia, also in stage A patients. Patients with deleted or mutated <em>ATM</em> had a significantly shorter treatment-free interval compared to patients without <em>ATM</em> alterations. <em>ATM</em>-mutated cases had a peculiar gene expression profile characterized by the deregulation of genes involved in apoptosis and DNA repair. Finally, definition of the structure of the <em>ATM</em>-mutated protein led to a hypothesis that functional abnormalities are responsible for the unfavorable clinical course of patients carrying these point mutations.<strong>Conclusions</strong> <em>ATM</em&gt; alterations are present at diagnosis in about 25% of individuals with chronic lymphocytic leukemia; these alterations are associated with a peculiar gene expression pattern and a shorter treatment-free interval.}, number={1}, journal={Haematologica}, author={Anna Guarini and Marilisa Marinelli and Simona Tavolaro and Emanuele Bellacchio and Monia Magliozzi and Sabina Chiaretti and Maria Stefania De Propris and Nadia Peragine and Simona Santangelo and Francesca Paoloni and Mauro Nanni and Ilaria Del Giudice and Francesca Romana Mauro and Isabella Torrente and Robin Foà}, year={2011}, month={Dec.}, pages={47-55} }