Ras pathway mutation feature in the same individuals at diagnosis and relapse of childhood acute lymphoblastic...

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, while relapse and refractory ALL remains a leading cause of death in children. However, paired ALL samples of initial diagnosis and relapse subjected to next-generation sequencing (NGS) could construct clonal lineage changes, and help to explore the key issues in the evolutionary process of tumor clones. Therefore, we aim to analyze gene alterations during the initial diagnosis and relapse of ALL patients and to explore the underlying mechanism.

Targeted exome sequencing technology was used to detect molecular characteristic of initial diagnosis and relapse of ALL in 12 pediatric patients. Clinical features, treatment response, prognostic factors and genetic features were analyzed.

In our 12 paired samples, 75% of pre-B-cell acute lymphoblastic leukemia (B-ALL) patients had alterations in the Ras pathway (NRAS, KRAS, NF1, and EPOR), and Ras mutation are very common in patients with ALL relapse. TP53 mutations mainly existed in the primary clones and occurred at the initial diagnosis and relapse of ALL. Relapse-associated genes such as NT5C2 and CREBBP were observed in patients with ALL relapse; however, all patients included in this study had gene abnormalities in the Ras pathway, and NT5C2 and CREBBP genes may collaboratively promote ALL relapse.

Among the 12 ALL patients, Ras pathway mutations are common in ALL relapse and may be associated with other recurrence-related genes alterations. The study with paired samples could improve the understanding of ALL relapse.