FRCPath Haem Part 1 MCQs-Mutation 484
A 68-year-old man is investigated for persistent neutrophilic leukocytosis. His WCC is 42 × 10⁹/L, with predominantly mature neutrophils and minimal left shift. There is no significant dysgranulopoiesis, blasts account for <1%, and he has moderate splenomegaly. BCR::ABL1 is not detected.
Which of the following mutations is most strongly associated with this condition?
A. SETBP1
B. ANKRD26
C. STAT5B
D. CSF3R
E. LMAN1
F. NBEAL2
Correct answer
D. CSF3R
Explanation
CSF3R mutations, particularly the activating CSF3R T618I mutation, are strongly associated with chronic neutrophilic leukaemia (CNL).
CNL is a rare BCR::ABL1-negative myeloid neoplasm characterised by persistent neutrophilic leukocytosis, predominantly mature neutrophils, minimal left shift, absence of significant dysgranulopoiesis and often splenomegaly.
The CSF3R T618I mutation causes constitutive activation of the granulocyte colony-stimulating factor receptor (G-CSFR) signalling pathway and is a key molecular feature supporting the diagnosis of CNL.
FRCPath exam pearl: CNL → CSF3R → T618I
The other options are associated with different haematological disorders:
SETBP1 – can occur in MDS/MPN with neutrophilia and other myeloid neoplasms.
ANKRD26 – associated with inherited thrombocytopenia.
STAT5B – associated with certain T-cell lymphoproliferative disorders and inherited immune abnormalities.
LMAN1…