Titin gene mutation is related to refractory acute lymphoblastic leukemia in children

This study aimed to elucidate the association of Titin ( TTN ) gene mutations with refractory pediatric acute lymphoblastic leukemia (ALL). This investigation, included 152 pediatric patients with ALL who were treated in Guangdong Provincial People’s Hospital between 2019 and 2023. All patients were subjected to morphology, immunology, cytology, and molecular biology (MICM) sub-typing. DNA was extracted from bone marrow for genetic testing via whole exome sequencing at the initial diagnosis or during disease progression. Furthermore, the clinical data from all the patients were collected, and the association of TTN gene mutations with these clinical features, minimal residual disease (MRD) levels, and glucocorticoid response were analyzed. Finally, the relationship between TTN gene mutations and progression-free survival (PFS) was investigated. Of the 152 patients, 23 (15.1%) were diagnosed with T-cell ALL (T-ALL), 25 (16.4%) with refractory disease, and 129 (84.9%) with B-cell ALL (B-ALL). Thirty-two (21.0%) had TTN + mutations, of which 8 had relapsed or refractory disease. Furthermore, the TTN+ children indicated prednisone resistance rates of 34.4%, while D15 MRD > 10% and D33 MRD > 0.1% values were 34.3% and 25.0% respectively. Whereas the TTN - children showed prednisone resistance rates of 17.5%, while D15 MRD > 10% and D33 MRD > 0.1% values were 15.8% and 10.0% respectively. Multivariate analysis (Logistic regression) indicated greater prednisone resistance and MRD non-optimal response in the TTN + group during induced treatment ( TTN + vs. TTN- , p < 0.05). In addition, the PFS analysis results demonstrated that the TTN + group had a higher incidence of early disease recurrence ( p < 0.05). However, there was no correlation between gene mutation and overall disease recurrence. These findings offer the inaugural evidence linking TTN mutation to refractory ALL. The data provide a reference for novel strategies against drug resistance.