Question

Which among the following is the most common tumour associated with neurofibromatosis in a child?

• A. Juvenile myelomonocytic leukemia
• B. Acute lymphoblastic leukemia
• C. Acute monocytic leukemia
• D. Acute myeloid leukemia

Hint:

NF1 loss drives the RAS pathway, and the RAS-driven childhood leukemia is JMML.

Answer 1

The Correct Option is A

Step 1: Recall the genetics of neurofibromatosis type 1 (NF1). NF1 is caused by loss of the NF1 gene, whose product neurofibromin is a negative regulator of the RAS signaling pathway. Loss of neurofibromin leads to unrestrained RAS activity.
Step 2: Link NF1 to hematologic malignancy. Among leukemias, the one most strongly tied to dysregulated RAS signaling in children is juvenile myelomonocytic leukemia (JMML), a clonal myeloproliferative/myelodysplastic disorder of early childhood.
Step 3: Apply the epidemiologic associations of JMML. About 80% of JMML cases carry an identifiable genetic abnormality in the RAS pathway: roughly 15 to 20% occur in children with NF1, about 25% have a RAS-family oncogene mutation, and about 35% have a PTPN11 mutation. NF1 children therefore have a markedly increased risk of JMML.
Step 4: Exclude the other leukemias. While ALL is the most common childhood leukemia overall, the leukemia specifically and characteristically associated with NF1 is JMML, not ALL, acute monocytic leukemia, or AML.
Conclusion: JMML is the leukemia most characteristically associated with neurofibromatosis in children. This matches the printed key (option A).