Genetic variants and clinical significance of pediatric acute lymphoblastic leukemia.

Background: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by molecular aberrations. Recently, genetic profiling has been fully investigated on ALL; however, the interaction between its genetic alterations and clinical features is still unclear. Therefore, we investigated the effects of genetic variants on ALL phenotypes and clinical outcomes.

Methods: Targeted exome sequencing technology was used to detect molecular profiling of 140 Chinese pediatric patients with ALL. Correlation of genetic features and clinical outcomes was analyzed.

Results: T-cell ALL (T-ALL) patients had higher initial white blood cell (WBC) count (34.8×10/L), higher incidence of mediastinal mass (26.9%), more relapse (23.1%), and enriched (23.1%), (23.1%) and (11.5%) mutations. Among the 18 recurrently mutated genes, and mutations occurred more in female patients (P=0.041), and mutants were with higher initial WBC counts (≥50×10/L) (P=0.047 and P=0.041), mutants were with higher minimal residual disease (MRD) level both on day 19 and day 46 (day 19 MRD ≥1%, P=0.039; day 46 MRD ≥0.01%, P=0.031) after induction chemotherapy. Multivariate analysis revealed that initial WBC counts (≥50×10/L), , and mutations were independent risk factors for 3-year relapse free survival (RFS) in ALL. Furthermore, mutations, age (<1 year or ≥10 years), and were independently associated with adverse outcome in B-cell ALL (B-ALL).

Conclusions: and mutations are powerful predictors for adverse outcome in pediatric B-ALL and ALL. Genetic profiling can contribute to the improvement of prognostication and management in ALL patients.