Nejvíce citovaný článek - PubMed ID 38314531
Unstable major molecular response as a trigger for next generation sequencing-based BCR::ABL1 mutation testing in chronic myeloid leukemia
Adolescent and young adults (AYAs) with chronic myeloid leukemia in chronic phase (CML-CP) reportedly respond worse to tyrosine kinase inhibitors (TKIs) than adults, potentially due to additional genetic abnormalities, including mutations in cancer-related genes (CRGs). This real-life study compared mutation profiles and their impact on outcomes in 80 AYA, 97 adult, and 16 pediatric CML-CP patients, alongside 81 BCR::ABL1-positive acute lymphoblastic leukemia (Ph+ ALL) patients. CRG mutations were more frequent in AYAs (25.0%) than in adults (19.6%) or children (12.5%). AYAs with Ph+ ALL exhibited higher mutational frequencies (53.3%) compared to children (26.7%) and adults (38.9%). At diagnosis, mutations in ASXL1, DNMT3A, and TET2 dominated in CML-CP and RUNX1, IKZF1, and BCR::ABL1 in Ph+ ALL. ASXL1 mutations correlated with reduced progression-free survival (PFS) in AYAs and adults. Unlike adults, AYAs showed no increase in BCR::ABL1 kinase domain mutations during TKI therapy. 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 exhibit worse prognoses than adults. Lower mutation rates at follow-up suggest potential impact of nilotinib. Mutation profiling and optimized TKI use are crucial to mitigate progression risks in CRG-mutated patients.
- MeSH
- akutní lymfatická leukemie * genetika farmakoterapie patologie mortalita MeSH
- bcr-abl fúzní proteiny * genetika MeSH
- chronická myeloidní leukemie * genetika farmakoterapie mortalita patologie MeSH
- dítě MeSH
- dospělí MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- nádorové biomarkery * genetika MeSH
- následné studie MeSH
- prognóza MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- ABL1 protein, human MeSH Prohlížeč
- bcr-abl fúzní proteiny * MeSH
- BCR-ABL1 fusion protein, human MeSH Prohlížeč
- inhibitory proteinkinas MeSH
- nádorové biomarkery * MeSH
- protoonkogenní proteiny c-abl MeSH
