title: What's different about atypical CML and chronic neutrophilic leukemia?
abstract: Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare myeloid neoplasms defined largely by morphologic criteria. The discovery of CSF3R mutations in aCML and CNL have prompted a more comprehensive genetic profiling of these disorders. These studies have revealed aCML to be a genetically more heterogeneous disease than CNL, however, several groups have reported that SETBP1 and ASXL1 mutations occur at a high frequency and carry prognostic value in both diseases. We also report a novel finding-our study reveals a high frequency of U2AF1 mutations at codon Q157 associated with CSF3R mutant myeloid neoplasms. Collectively, these findings will refine the WHO diagnostic criteria of aCML and CNL and help us understand the genetic lesions and dysregulated signaling pathways contributing to disease development. Novel therapies that emerge from these genetic findings will need to be investigated in the setting of a clinical trial to determine the safety and efficacy of targeting various oncogenic drivers, such as JAK1/2 inhibition in CSF3R-T618I-positive aCML and CNL. In summary, recent advances in the genetic characterization of CNL and aCML are instrumental toward the development of new lines of therapy for these rare leukemias that lack an established standard of care and are historically associated with a poor prognosis.
authors.affiliation: Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR; and.
authors.forename: Kim-Hien T
authors.initials: KH
authors.lastname: Dao
authors.affiliation: Knight Cancer Institute, Department of Cell, Development and Cancer Biology, Oregon Health & Science University, Portland, OR.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Tyner
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D003062:Codon; D006405:Hematology / Q000379:methods / Q000592:standards; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis* / Q000235:genetics; D015467:Leukemia, Neutrophilic, Chronic / Q000175:diagnosis* / Q000235:genetics; D008495:Medical Oncology / Q000379:methods / Q000592:standards; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D015398:Signal Transduction; D000072668:Splicing Factor U2AF
chemical_list: C473949:ASXL1 protein, human; C517047:CSF3R protein, human; D002352:Carrier Proteins; D003062:Codon; D009687:Nuclear Proteins; D016184:Receptors, Colony-Stimulating Factor; D012097:Repressor Proteins; D012261:Ribonucleoproteins; C425066:SETBP1 protein, human; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human