What mutation is commonly associated with chronic neutrophilic leukemia?

Chronic neutrophilic leukemia (CNL) is primarily associated with mutations in the CSF3R gene, which encodes the receptor for granulocyte colony-stimulating factor (G-CSF). The mutation in CSF3R leads to constitutive activation of the signaling pathways that promote the proliferation and survival of neutrophil precursors in the bone marrow. This results in excessive production of neutrophils, hallmark of CNL.

While mutations in FLT3, TP53, and JAK2 are significant in other myeloid malignancies, they are not directly linked to chronic neutrophilic leukemia. FLT3 mutations are often associated with acute myeloid leukemia, TP53 mutations are common in various cancers and can indicate poor prognosis, and JAK2 mutations are typically linked to myeloproliferative neoplasms, particularly polycythemia vera and essential thrombocythemia. Thus, the specific presence of mutations in CSF3R is a defining characteristic of chronic neutrophilic leukemia.