title: Leukemic transformation driven by an ASXL1 mutation after a JAK2V617F-positive primary myelofibrosis: clonal evolution and hierarchy revealed by next-generation sequencing.
abstract: We have characterized the molecular changes underlying the transformation of a JAK2V617F+-myelofibrosis with trisomy 8, into a JAK2V617F-negative leukemia. Leukemic clone did not carry JAK2V617F mutation, but showed ASXL1 mutation (R693X). This mutation was identified in a low percentage at diagnosis by next-generation sequencing. Using this technology in serial specimens during the follow-up, we observed a progressive expansion of the ASXL1-mutated minor clone, whereas the JAK2V617F+-clone carrying trisomy 8 decreased. Hematologic progression occurred simultaneously with an ASXL1-R693X-negative lung-cancer. This is the first report showing a clear association between the expansion of an ASXL1-mutated clone and the leukemic transformation of myelofibrosis.
authors.affiliation: Hematology and Medical Oncology Unit, Hospital Universitario Morales-Meseguer, Centro Regional de Hemodonación, C/Ronda de Garay, sn, 3003, Murcia, Spain. fferrermarin@gmail.com.
authors.forename: Francisca
authors.initials: F
authors.lastname: Ferrer-Marín
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Luz
authors.initials: L
authors.lastname: Martínez-Avilés
authors.forename: Gloria
authors.initials: G
authors.lastname: Soler
authors.forename: Pablo
authors.initials: P
authors.lastname: Carbonell
authors.forename: Ginés
authors.initials: G
authors.lastname: Luengo-Gil
authors.forename: Eva
authors.initials: E
authors.lastname: Caparrós
authors.forename: José M
authors.initials: JM
authors.lastname: Torregrosa
authors.forename: Carlos
authors.initials: C
authors.lastname: Besses
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
mesh_terms: D002471:Cell Transformation, Neoplastic; D002898:Chromosomes, Human, Pair 8; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014314:Trisomy / Q000235:genetics
chemical_list: C473949:ASXL1 protein, human; D012097:Repressor Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2