Introduction
Juvenile myelomonocytic leukemia (JMML) is one of the rarest pediatric hematologic malignancies, affecting around 1.2 per million children per year1. It usually occurs in early childhood and possesses a dismal prognosis2. Ninety percent of cases with JMML could be attributed to alterations involving RAS/MAPKsignaling pathway, including KRAS , NRAS , PTPN11 ,NF1 , and CBL 3. Hematopoietic stem cell transplantation (HSCT) has been regarded as the only cure for patients with JMML2. However, some specific subtypes, such as germline CBL -mutated JMML or JMML with clonal RASmutations, portrayed a less aggressive picture and even displayed spontaneous remission4-7. As a result, determining the culpable molecular aberrancy is curial in the management of patients with JMML. With the booming development of next-generation sequencing (NGS) in the field of hematologic malignancies, the underlying genomic alterations of neoplastic diseases are more easily accessible nowadays. However, NGS also discovers genetic changes with unknown influences on protein function or clinical pathogenicity, termed variant of uncertain significance (VUS)8. In clinical practices, a VUS usually brings challenges to the physicians because of the inadequacy of clinical information for decision-making. We report our experience in taking care of a child with JMML concurrently harboring a germlineCBL pathogenic mutation and a germline NF1 VUS.