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.