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

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

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)167-176
Number of pages10
Issue number1
Publication statusPublished - Jul 7 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Klampfl, T., Harutyunyan, A., Berg, T., Gisslinger, B., Schalling, M., Bagienski, K., Olcaydu, D., Passamonti, F., Rumi, E., Pietra, D., Jäger, R., Pieri, L., Guglielmelli, P., Iacobucci, I., Martinelli, G., Cazzola, M., Vannucchi, A. M., Gisslinger, H., & Kralovics, R. (2011). Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood, 118(1), 167-176.