title: Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time.
abstract: MPLW515L/K and JAK2V617F can co-exist in myelofibrosis with myeloid metaplasia (MMM). The chronology of clonal emergence was studied in three such cases using serially stored bone marrow. At diagnosis, a major MPL515 mutant clone was accompanied by a minor JAK2V617F clone in all three instances. At 25 time points over a period of 4-8 years, allele burden fluctuated but remained high for MPLW515L/K and low for JAK2V617F. We conclude that MPLW515L/K and JAK2V617F are both early events in MMM and allele burden, rather than the mere presence of these mutations, might be relevant to phenotypic variation in myeloproliferative disorders.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: McClure
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000483:Alleles; D001854:Bone Marrow Cells; D002845:Chromatography; D002999:Clone Cells; D004247:DNA / Q000032:analysis; D005787:Gene Frequency; D006098:Granulocytes; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D055728:Primary Myelofibrosis / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D013922:Thrombocytosis / Q000235:genetics; D013995:Time
chemical_list: D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D004247:DNA; C507924:JAK2 protein, human; D053614:Janus Kinase 2