Clinical Impact of MTAP Rearrangement in Pediatric Acute Lymphoblastic Leukemia: Insights From Whole Transcriptome Analysis.
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OBJECTIVE: To investigate the distribution and molecular characteristics of MTAP rearrangements in pediatric acute lymphoblastic leukemia (ALL) and assess their impact on clinical features, treatment response, and prognosis. METHODS: We retrospectively analyzed 338 pediatric ALL patients. Patients were stratified into two cohorts based on MTAP rearrangement status: the MTAP-r group and the non-MTAP-r group. Baseline clinical characteristics, molecular profiles, and induction therapy responses were compared between the groups. Prognostic outcomes were also evaluated. RESULTS: Among the 338 pediatric ALL patients, 32 (9.47%) harbored MTAP rearrangements. Compared to the non-MTAP-r group, patients in the MTAP-r group demonstrated a significantly higher proportion of T-ALL (p < 0.05), elevated peripheral WBC counts at diagnosis, higher LDH levels, and were more frequently classified into intermediate-/high-risk groups (p < 0.05). Five distinct MTAP rearrangement patterns were identified, with MTAP::CDKN2B-AS1 being the most prevalent (75.0%). Regarding mutational profiles, MTAP-r patients exhibited a higher frequency of mutations in NOTCH1, PTEN, FBXW7, SRCAP, and USP7. Furthermore, the mutated genes were significantly enriched in pathways related to viral carcinogenesis, immune evasion, and metabolic signaling. Patients with MTAP-r ALL exhibited significantly inferior outcomes compared to those in the non-MTAP-r group. CONCLUSION: MTAP rearrangement defines a distinct and clinically adverse subset of pediatric ALL characterized by specific fusion architecture and an unfavorable co-mutation pattern. Beyond its diagnostic value, MTAP-r represents a promising biomarker for trial enrollment and future risk-adapted strategies. Confirmation of independent prognostic impact and therapeutic utility will require multivariable analyses and prospective, biomarker-driven studies.