0013750 2026 RIV GB eng J
Křížková, Jitka - Polívková, Václava - Láznička, Adam - Čuřík, Nikola - Broučková, Adéla - Suchánková, Pavla - Smažík, Tomáš - Vyšínová, Veronika - Mikulenková, Dana - Klamová, Hana - Šťastná Marková, Markéta - Srbová, Dana - Zuna, J. - Žaliová, M. - Trka, J. - Šálek, Cyril - Šálek, Cyril - Machová Poláková, Kateřina^G
Somatic mutations and outcomes in chronic myeloid leukemia adolescent and young adults compared to children, adults, and BCR::ABL1-positive acute lymphoblastic leukemia.
Leukemia. Vol. 39, no. April (2025), art. no. 28789. ISSN 0887-6924
Grant: Ministerstvo zdravotnictví NU21-07-00225; Ministerstvo školství, mládeže a tělovýchovy LM2023033
Institucionální podpora: RVO:00023736
Klíčová slova: somatic mutations * eryhtropoiesis * CML
Cite Score: 18.500, rok: 2024; SJR: 3.458, rok: 2024; IF: 13.4, rok: 2024
DOI: 10.1038/s41375-025-02609-3

Anotace: Adolescent and young adult (AYA) patients with chronic myeloid leukemia in chronic phase (CML-CP) reportedly fare worse on tyrosine kinase inhibitor (TKIs) than adults. This real-life study compared mutation profiles and outcomes in 80 AYA, 97 adult, and 16 pediatric CML-CP patients, alongside 81 BCR::ABL1-positive acute lymphoblastic leukemia (ALL) patients. Somatic mutations in cancer-related genes (CRGs) were more frequent in AYAs with CML-CP (25.0%) than in adults (19.6%) or children (12.5%). AYAs with Ph+ ALL also exhibited higher mutational frequencies (53.3%) compared to children (26.7%) and adults (38.9%). Mutation landscapes differed at diagnosis with ASXL1, DNMT3A, and TET2dominant in CML-CP and RUNX1, IKZF1, and BCR::ABL1predominated in Ph+ ALL. ASXL1 mutations correlated with reduced progression-free survival (PFS) in AYAs and adults, with adults showing increased BCR::ABL1 mutations during TKI therapy, a trend not observed in AYAs. Nilotinib improved PFS in AYAs with ASXL1 mutations, highlighting the efficacy of higher-generation TKIs. ASXL1 mutations also impaired erythropoiesis, warranting further validation. Despite a higher mutational burden, AYAs did not show worse prognoses than adults, with lower mutation rates at follow-up suggesting better adherence. Mutation profiling and optimized TKI use are crucial to mitigate progression risks in CRG-mutated patients.