title: Molecular analyses of 15,542 patients with suspected BCR-ABL1-negative myeloproliferative disorders allow to develop a stepwise diagnostic workflow.
abstract: We investigated 15,542 patients with suspected BCR-ABL1- negative myeloproliferative or myelodysplastic/myeloproliferative neoplasm (including 359 chronic myelomonocytic leukemia) by a molecular marker set. JAK2V617F was detected in the suspected categories as follows: polycythemia vera 88.3%, primary myelofibrosis 53.8%, essential thrombocythemia 50.2%, and not further classifiable myeloproliferative neoplasms 38.0%. JAK2 exon 12 mutations were detected in 40.0% JAK2V617F-negative suspected polycythemia vera, MPLW515 mutations in 13.2%JAK2V617F-negative primary myelofibrosis and 7.1% JAK2V617F-negative essential thrombocythemia. TET2 mutations were distributed across all entities but were most frequent in suspected chronic myelomonocytic leukemia (77.8%). CBL mutations were identified in suspected chronic myelomonocytic leukemia (13.9%), primary myelofibrosis (8.0%), and not further classifiable myeloproliferative neoplasm (7.0%). This leads to a stepwise workflow for suspected myeloproliferative neoplasms starting with JAK2V617F and investigating JAK2V617F-negative patients for JAK2 exon 12 or MPL mutations, respectively. In cases in which a myeloproliferative neoplasm cannot be established, analysis for TET2, CBL and EZH2 mutations may be indicated.
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany. susanne.schnittger@mll.com
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Christiane
authors.initials: C
authors.lastname: Eder
authors.forename: Frank
authors.initials: F
authors.lastname: Dicker
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.forename: Vera
authors.initials: V
authors.lastname: Grossmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Kohlmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005091:Exons; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D007223:Infant; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis* / Q000235:genetics*; D057188:Workflow; D055815:Young Adult
chemical_list: D016044:Fusion Proteins, bcr-abl; D053614:Janus Kinase 2