title: Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia.
abstract: Chronic neutrophilic leukemia (CNL) and chronic myelomonocytic leukemia (CMML) are rare hematologic neoplasms. We performed CSF3R, SRSF2 and SETBP1 mutational analyses in 10 CNL and 56 CMML patients. In this sample cohort, 80% of CNL patients harbored CSF3R mutations, of which the CSF3R T618I mutation was dominant. Mutations in CSF3R and SETBP1 were found in 7.1% and 5.3% CMML patients respectively, while 25% of CMML patients carried SRSF2 mutations. Strikingly, we identified that all of the CSF3R mutations detected in CMML patients were represented by a P733T mutation. The CSF3R P733T mutation represents a novel CSF3R mutation. In addition, none of the four CSF3R P733T mutated patients carried SRSF2 mutations [0/14 (0%) patients with combined CSF3R P733T and SRSF2 mutations vs. 4/42 (9.5%) with CSF3R P733T and wt SRSF2, P < 0.001]. Both mut SRSF2 and mut SETBP1 patients had shorter overall survival (OS) and progression-free survival (PFS) compared to patients with wt SRSF2 (P < 0.001 both) and wt SETBP1 (P < 0.001 and P = 0.02, respectively). While we found no significant differences in OS and PFS as a consequence of CSF3R mutation status, our work suggest that the CSF3R T618I mutation is a diagnostic marker with good specificity and sensitivity for CNL. In conclusion, our study highlights effective diagnostic and prognostic markers of CNL and CMML patients in the Chinese population.
authors.affiliation: Department of Hematology, Ruijin Hospital North Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China.|Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Qiao
authors.affiliation: Department of Hematology, Ruijin Hospital North Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology, Ruijin Hospital North Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China.|Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Su-Jiang
authors.initials: SJ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics* / Q000473:pathology; D015467:Leukemia, Neutrophilic, Chronic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C517047:CSF3R protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D016184:Receptors, Colony-Stimulating Factor; C425066:SETBP1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors
keywords: CMML; CNL; CSF3R; SRSF2; gene mutation