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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10497611" target="_blank" >RIV/00064203:_____/25:10497611 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10497611 RIV/00216208:11130/25:10497611

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=eXiCBzOVH4" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=eXiCBzOVH4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41375-025-02609-3" target="_blank" >10.1038/s41375-025-02609-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Leukemia

ISSN

0887-6924

e-ISSN

1476-5551

Svazek periodika

39

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

1670-1677

Kód UT WoS článku

001477685600001

EID výsledku v databázi Scopus

2-s2.0-105003742144