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.