title: Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm.
abstract: Myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These disorders may undergo phenotypic shifts, and may specifically evolve into secondary myelofibrosis (MF) or acute myeloid leukemia (AML). We studied genomic changes associated with these transformations in 29 patients who had serial samples collected in different phases of disease. Genomic DNA from granulocytes, i.e., the myeloproliferative genome, was processed and hybridized to genome-wide human SNP 6.0 arrays. Most patients in chronic phase had chromosomal regions with uniparental disomy (UPD) and/or copy number changes. Disease progression to secondary MF or AML was associated with the acquisition of additional chromosomal aberrations in granulocytes (P = 0.002). A close relationship was observed between aberrations of chromosome 9p (UPD and/or gain) and progression from PV to post-PV MF (P = 0.002). The acquisition of one or more aberrations involving chromosome 5, 7, or 17p was specifically associated with progression to AML (OR 5.9, 95% CI 1.2-27.7, P = 0.006), and significantly affected overall survival (HR 18, 95% CI 1.9-164, P = 0.01). These observations indicate that disease progression from chronic-phase MPN to secondary MF or AML is associated with specific chromosomal aberrations that can be detected by means of high-resolution SNP array analysis of granulocyte DNA.
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. elisarumi@hotmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.forename: Ashot
authors.initials: A
authors.lastname: Harutyunyan
authors.forename: Chiara
authors.initials: C
authors.lastname: Elena
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietra
authors.forename: Thorsten
authors.initials: T
authors.lastname: Klampfl
authors.forename: Klaudia
authors.initials: K
authors.lastname: Bagienski
authors.forename: Tiina
authors.initials: T
authors.lastname: Berg
authors.forename: Ilaria
authors.initials: I
authors.lastname: Casetti
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D001752:Blast Crisis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007558:Italy; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D011087:Polycythemia Vera / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D055728:Primary Myelofibrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000209:etiology / Q000235:genetics / Q000378:metabolism
chemical_list: D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D004247:DNA; C507924:JAK2 protein, human; D053614:Janus Kinase 2