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We evaluated the effects of\n                    <jats:italic>ATM<\/jats:italic>\n                    aberrations (del(11q) and\/or\n                    <jats:italic>ATM<\/jats:italic>\n                    mutations) on time-to-first-treatment (TTFT) in 3631 untreated patients with CLL, in the context of IGHV gene mutational status and mutations in nine CLL-related genes.\n                    <jats:italic>ATM<\/jats:italic>\n                    mutations were present in 246 cases (6.8%), frequently co-occurring with del(11q) (112\/246 cases, 45.5%).\n                    <jats:italic>ATM<\/jats:italic>\n                    -mutated patients displayed a different spectrum of genetic abnormalities when comparing IGHV-mutated (M-CLL) and unmutated (U-CLL) cases: M-CLL was enriched for\n                    <jats:italic>SF3B1<\/jats:italic>\n                    and\n                    <jats:italic>NFKBIE<\/jats:italic>\n                    mutations, whereas U-CLL showed mutual exclusivity with trisomy 12 and\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations. Isolated\n                    <jats:italic>ATM<\/jats:italic>\n                    mutations were rare, affecting 1.2% of Binet A patients and &lt;1% of M-CLL cases. While univariable analysis revealed shorter TTFT for Binet A patients with any\n                    <jats:italic>ATM<\/jats:italic>\n                    aberration compared to\n                    <jats:italic>ATM<\/jats:italic>\n                    -wildtype, multivariable analysis identified only del(11q), trisomy 12,\n                    <jats:italic>SF3B1<\/jats:italic>\n                    , and\n                    <jats:italic>EGR2<\/jats:italic>\n                    mutations as independent prognosticators of shorter TTFT among Binet A patients and within M-CLL and U-CLL subgroups. These findings highlight del(11q), and not\n                    <jats:italic>ATM<\/jats:italic>\n                    mutations, as a key biomarker of increased risk of early progression and need for therapy, particularly in otherwise indolent M-CLL, providing insights into risk-stratification and therapeutic decision-making.\n                  <\/jats:p>","DOI":"10.1038\/s41375-025-02615-5","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:30:53Z","timestamp":1745472653000},"page":"1650-1660","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["ATM aberrations in chronic lymphocytic leukemia: del(11q) rather than ATM mutations is an adverse-prognostic 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Research funding: AbbVie, Gilead, Janssen, Novartis, Sunesis; LS: advisory board AbbVie, AstraZeneca, Janssen; RR: honoraria\/advisory board: AbbVie, AstraZeneca, Illumina, Janssen, Lilly and Roche; KS: honoraria\/advisory board: AbbVie, Acerta\/AstraZeneca, Gilead, Janssen. Research funding: AbbVie, Gilead, Janssen; PB: honoraria from Abbvie, Gilead and Janssen. Research funding from Gilead; GG: Advisory Board\/Speaker\u2019s bureau: Abbvie, AstraZeneca, Beigene, Hikma, Incyte, Johnson & Johnson, Lilly; LB: honoraria\/advisory board: Abbvie, Amgen, Astellas, BMS\/Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics. Research funding: Bayer, Jazz Pharmaceuticals; GMR: honoraria from Abbvie, AstraZeneca, Gilead and Janssen. Research funding from Gilead; CB: Honoraria\/advisory board: AstraZeneca and Eli Lilly. CUN received research grants and\/or honoraria from Abbvie, AstraZeneca, Janssen, Genmab, Beigene, Octapharma, MSD, Lilly, Synamics, CSL Behring, Takeda, Nofo Nordisk Foundation. The other authors declare no competing financial interests","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}