Identification of a novel MEF2C::SS18L1 fusion in childhood acute B-lymphoblastic leukemia.

PURPOSE: Leukemia-associated fusion genes are closely related to the occurrence, development, diagnosis, and treatment of leukemia. DNA microarrays and second-generation sequencing have discovered multiple B-ALL fusion genes. We identified a novel MEF2C::SS18L1 fusion gene in a child diagnosed with B-ALL. This study investigates the oncogenicity and prognosis of this fusion gene in B-ALL. METHODS: A child with B-ALL who has a MEF2C::SS18L1 fusion is reported as a newly discovered case. Compared the breakpoints, structural domains, clinical phenotypes, and differential expression genes of MEF2C::SS18L1 and MEF2D::SS18.Using "ONCOFUSE" software, the carcinogenicity of MEF2C::SS18L1 is predicted. Using whole transcriptome sequencing, we analyze the breakpoints and the secondary structure of the fusion protein. Further, we compared the structures, differentially expressed genes, and clinical phenotypes of MEF2D and MEF2C fusion genes by DESeq, GO functional enrichment, and flow cytometry immunophenotyping analysis. RESULTS: Whole transcriptome sequencing identified a MEF2C::SS18L1 fusion transcript in a 3-year-old child with B-ALL. The MADS box, MEF structural domain, HJURP_C structural domain, and TAD I structural domain of MEF2C, and the QPGY structural domain of SS18L1, make up the fusion protein. "Oncofuse" found a 0.99 Bayesian probability that the fusion gene drives cancer. The breakpoint positions, fusion protein secondary structures, differentially expressed genes, and clinical characteristics of this patient were identical to those with MEF2D::SS18 fusion gene. CONCLUSION: We identified a novel MEF2C::SS18L1 fusion gene in childhood ALL, which shares similar structural and clinical characteristics with MEF2D::SS18. Further studies with more samples should be conducted in future.

Modified SMILE (mSMILE) is active in the treatment of pediatric Epstein-Barr virus-associated natural killer/T-cell lymphoma: a single center experience, case series.

Background: The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes. Methods: In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle. Results: Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy. Conclusions: Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.

Health-related quality of life in children with childhood acute myeloid leukemia in China: A five-year prospective study.

Purpose: This study aims to identify the key factors influencing health-related quality of life (HRQoL) of pediatric acute myeloid leukemia (AML) patients following their initial diagnosis and examine their impact on the five-year survival prognosis. Methods: A chart review and follow-up were conducted for children with AML who participated in a prospective cohort study between 2017 and 2020. We identified factors influencing HRQoL through Pediatric Quality of Life Inventory™ (PedsQL™ 4.0), PedsQL™ Cancer Module 3.0 (CM 3.0) and PedsQL™ Family Impact Module 2.0 (FIM 2.0), as well as assessed the impact of impaired HRQoL on the overall outcomes of patients. Results: Sixty-four subjects enrolled in the study had complete HRQoL outcome data, and 61 of them completed the 5-year follow-up. In CM 3.0, age was positively associated with parental proxy reports (p = 0.040), whereas divorced families were negatively associated with child self-reports (p = 0.045). A positive medical history correlates with FIM 2.0 (p = 0.025). Residence (p = 0.046), the occupation of caregivers (p = 0.014), disease severity (p = 0.024), and the only child (p = 0.029) exhibited statistically significant associations with the impairment of HRQoL. Impaired HRQoL scores shown by the PedsQL™4.0 parent proxy report (p = 0.013) and FIM 2.0 (p = 0.011) were associated with a reduced 5-year survival rate. Conclusions: This study demonstrated that early impairment of HRQoL in pediatric acute myeloid leukemia patients has predictive value for long-term prognosis. Once validated, these findings may provide some guidance to clinicians treating children with AML.