Clinical and molecular characterization of patients with juvenile myelomonocytic leukaemia

Summary Juvenile myelomonocytic leukaemia (JMML) is a rare haematological malignancy caused by mutations in the Ras signalling pathway. Next‐generation sequencing (NGS) and DNA methylation profiling used for diagnostic and risk stratification purposes are now standard of care in Europe and the United States for patients with JMML. To better understand how implementing these types of technologies would impact the treatment of JMML patients in different settings, molecular profiling was performed on 81 patients treated for JMML in Egypt from 2009 to 2022. NGS increased the number of patients with a molecular diagnosis compared to conventional Sanger sequencing. NGS and DNA methylation analysis also identified patients with a higher risk for relapse based on the presence of multiple mutations or intermediate/high methylation respectively. Mutational burden, cytogenetics and methylation subgrouping were combined to develop a risk stratification model that may help to prioritize patients for haematopoietic stem cell transplantation. In summary, advanced molecular testing is key to enabling an accurate diagnosis and predicting outcome in JMML.