Clonal evolution in a chronic neutrophilic leukemia patient

ABSTRACT Objectives and importance: Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm with a high prevalence (>80%) of mutations in the colony-stimulating factor 3 receptor (CSF3R); these mutations activate the receptor, leading to the proliferation of neutrophils that are a hallmark of CNL. Clinical presentation: We present a male patient who presented peripheral blood leukocytosis. On the basis of his morphological appearances and molecular findings he was determined to have a diagnosis of chronic neutrophilic leukemia. At a follow-up at 7 months, in addition to the CSF3R c.2373G？>？A (p.W791*) truncated mutation, another CSF3R mutation appeared as c.1853C？>？T(p.T618I). Discussion and conclusion: We present the first patient with a diagnosis of chronic neutrophilic leukemia with a c.2373G？>？A (p.W791*) truncated mutation of CSF3R. These findings elucidate a novel paradigm of CNL pathogenesis and explain how mutations drive the development of the disease. The order of acquisition of CSF3R mutations relative to mutations in epigenetic modifiers and the spliceosome have been determined only in isolated case reports; thus, further work is needed to understand the impact of mutation chronology on the clonal evolution and progression of CNL