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<p>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 <i>BCR::ABL1</i>-positive acute lymphoblastic leukemia (Ph+&#xa0;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 <i>ASXL1</i>, <i>DNMT3A</i>, and <i>TET2</i> dominated in CML-CP and <i>RUNX1</i>, <i>IKZF1</i>, and <i>BCR::ABL1</i> in Ph+ ALL. <i>ASXL1</i> mutations correlated with reduced progression-free survival (PFS) in AYAs and adults. Unlike adults, AYAs showed no increase in <i>BCR::ABL1</i> kinase domain mutations during TKI therapy. Nilotinib improved PFS in AYAs with <i>ASXL1</i> mutations, highlighting the efficacy of higher-generation TKIs. <i>ASXL1</i> 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.</p><p></p>

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Somatic mutations and outcomes in chronic myeloid leukemia adolescent and young adults compared to children, adults, and BCR::ABL1-positive acute lymphoblastic leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月28日

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  • Jitka Krizkova,
  • Vaclava Polivkova,
  • Adam Laznicka,
  • Nikola Curik,
  • Adela Benesova,
  • Pavla Suchankova,
  • Tomas Smazik,
  • Veronika Vysinova,
  • Dana Mikulenkova,
  • Hana Klamova,
  • Marketa Stastna Markova,
  • Dana Srbova,
  • Jan Zuna,
  • Marketa Zaliova,
  • Jan Trka,
  • Cyril Salek,
  • Katerina Machova Polakova

摘要

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.