Molecular Aberrations of Chronic Neutrophilic Leukemia: The CSF3R and SETBP1 Mutations

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by sustained elevated neutrophil levels with <10% immature cells according to WHO criteria. Recently, oncogenic mutations affecting the granulocyte-colony stimulating factor receptor (CSF3R) were reported to be highly prevalent in CNL. SET binding protein 1(SETBP1) mutations were also reported in some CNL cases. We reviewed clinical suspected 12 “CNL” patients and performed CSF3R and SETBP1 sequencing. All the 6 who met WHO criteria for CNL carried CSF3R T618I mutation. Four of the 6 also had SETBP1 mutations and a 5th had a CALR mutation (c.1154-1155insTTGTC). Two other who met these criteria but also had monoclonal gammopathy with uncertain significance (MGUS) had no CSF3R, SETBP1 or CALR mutation. The rest 4 carried infection or tumor and thus were excluded. We conclude including CSF3R and SETBP1 mutations into WHO criteria for CNL may improve diagnostic accuracy and may have therapeutic implications.