title: SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations.
abstract: Chronic myeloid malignancies are categorized to the three main categories myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs) and MDS/MPN overlap. So far, no specific genetic alteration profiles have been identified in the MDS/MPN overlap category. Recent studies identified mutations in SET-binding protein 1 (SETBP1) as novel marker in myeloid malignancies, especially in atypical chronic myeloid leukemia (aCML) and related diseases. We analyzed SETBP1 in 1 130 patients with MPN and MDS/MPN overlap and found mutation frequencies of 3.8% and 9.4%, respectively. In particular, there was a high frequency of SETBP1 mutation in aCML (19/60; 31.7%) and MDS/MPN unclassifiable (MDS/MPN, U; 20/240; 9.3%). SETBP1 mutated (SETBP1mut) patients showed significantly higher white blood cell counts and lower platelet counts and hemoglobin levels than SETBP1 wild-type patients. Cytomorphologic evaluation revealed a more dysplastic phenotype in SETBP1mut cases as compared with wild-type cases. We confirm a significant association of SETBP1mut with -7 and isochromosome i(17)(q10). Moreover, SETBP1mut were strongly associated with ASXL1 and CBL mutations (P<0.001 for both) and were mutually exclusive of JAK2 and TET2 mutations. In conclusion, SETBP1mut add an important new diagnostic marker for MDS/MPN and in particular for aCML.
authors: MLL Munich Leukemia Laboratory, Munich, Germany.
authors: M
authors: M
authors: Meggendorfer
authors: U
authors: U
authors: Bacher
authors: T
authors: T
authors: Alpermann
authors: C
authors: C
authors: Haferlach
authors: W
authors: W
authors: Kern
authors: C
authors: C
authors: Gambacorti-Passerini
authors: T
authors: T
authors: Haferlach
authors: S
authors: S
authors: Schnittger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D018404:Isochromosomes; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C425066:SETBP1 protein, human; D050721:Proto-Oncogene Proteins c-cbl