USP7 mutations are associated with adverse outcomes in pediatric T cell acute lymphoblastic leukemia and lymphoma

Area of Science:

• Oncology
• Genetics
• Pediatric Hematology/Oncology

Background:

• Understanding genetic alterations in pediatric T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is crucial for improving treatment strategies.
• The role of USP7 alterations in T-ALL/LBL prognosis is not fully understood.

Purpose of the Study:

• To investigate the clinical features and long-term outcomes of pediatric T-ALL/LBL patients with USP7 mutations.
• To evaluate the prognostic significance of USP7 mutations, alone and in combination with NOTCH1 mutations.

Main Methods:

• Sanger sequencing was used to detect USP7 and NOTCH1 mutations in 313 pediatric T-ALL/LBL patients.
• Cox regression and nomogram models were employed to assess prognostic importance.
• Event-free survival (EFS) and overall survival (OS) were analyzed.

Main Results:

• USP7 mutations were identified in 12 patients, associated with older age and lower remission rates at day 15.
• Patients with USP7 mutations exhibited significantly worse EFS and OS.
• Concurrent analysis revealed USP7^mutNOTCH1^wt genotype correlated with the worst outcomes, while USP7^wtNOTCH1^mut showed the best outcomes.
• USP7 mutation, high MRD, and CNS leukemia were independent adverse prognostic factors.

Conclusions:

• USP7 mutations identify a subset of pediatric T-ALL/LBL patients with adverse outcomes.
• USP7 mutation status is a highly influential prognostic factor, enhancing prediction model accuracy.
• Incorporating USP7 mutation status into risk stratification may refine treatment decisions for T-ALL/LBL.