Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression.

نویسندگان

  • Thorsten Klampfl
  • Ashot Harutyunyan
  • Tiina Berg
  • Bettina Gisslinger
  • Martin Schalling
  • Klaudia Bagienski
  • Damla Olcaydu
  • Francesco Passamonti
  • Elisa Rumi
  • Daniela Pietra
  • Roland Jäger
  • Lisa Pieri
  • Paola Guglielmelli
  • Ilaria Iacobucci
  • Giovanni Martinelli
  • Mario Cazzola
  • Alessandro M Vannucchi
  • Heinz Gisslinger
  • Robert Kralovics
چکیده

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are clonal myeloid disorders with increased production of terminally differentiated cells. The disease course is generally chronic, but some patients show disease progression (secondary myelofibrosis or accelerated phase) and/or leukemic transformation. We investigated chromosomal aberrations in 408 MPN samples using high-resolution single-nucleotide polymorphism microarrays to identify disease-associated somatic lesions. Of 408 samples, 37.5% had a wild-type karyotype and 62.5% harbored at least 1 chromosomal aberration. We identified 25 recurrent aberrations that were found in 3 or more samples. An increased number of chromosomal lesions was significantly associated with patient age, as well as with disease progression and leukemic transformation, but no association was observed with MPN subtypes, Janus kinase 2 (JAK2) mutational status, or disease duration. Aberrations of chromosomes 1q and 9p were positively associated with disease progression to secondary myelofibrosis or accelerated phase. Changes of chromosomes 1q, 7q, 5q, 6p, 7p, 19q, 22q, and 3q were positively associated with post-MPN acute myeloid leukemia. We mapped commonly affected regions to single target genes on chromosomes 3p (forkhead box P1 [FOXP1]), 4q (tet oncogene family member 2 [TET2]), 7p (IKAROS family zinc finger 1 [IKZF1]), 7q (cut-like homeobox 1 [CUX1]), 12p (ets variant 6 [ETV6]), and 21q (runt-related transcription factor 1 [RUNX1]). Our data provide insight into the genetic complexity of MPNs and implicate new genes involved in disease progression.

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منابع مشابه

MYELOID NEOPLASIA Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression

1Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; 2Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria; 3Division of Hematology, Azienda Ospedaliera Universitaria Fondazione Macchi, Varese, Italy; 4Department of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico ...

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عنوان ژورنال:
  • Blood

دوره 118 1  شماره 

صفحات  -

تاریخ انتشار 2011