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

Solve this by following the molecular pathway that NF1 disrupts. The NF1 gene encodes neurofibromin, a GTPase-activating protein that switches off RAS; when NF1 is lost, RAS stays active and drives excessive proliferation of myeloid progenitors. The childhood leukemia that is fundamentally a disease of hyperactive RAS signaling is juvenile myelomonocytic leukemia, an aggressive clonal disorder of infancy and early childhood that blends myelodysplastic and myeloproliferative features. The strength of this link is reflected in the mutation spectrum of JMML: the overwhelming majority of patients harbor a lesion somewhere along the RAS axis, including a substantial fraction with germline NF1, others with activating RAS oncogene mutations, and a large group with PTPN11 (SHP2) mutations, all of which converge on the same overactive pathway. The distractors do not share this mechanistic tie. Acute lymphoblastic leukemia, although the commonest pediatric leukemia in the general population, is not the NF1-defining malignancy, and acute monocytic and acute myeloid leukemias are not the classic NF1 association either. Because the question asks specifically about the tumour linked to neurofibromatosis, the RAS-pathway leukemia is the answer. $\text{NF1 loss} \rightarrow \uparrow \text{RAS} \rightarrow \text{JMML}$.\[\boxed{\text{Juvenile myelomonocytic leukemia}}\]