Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression
| Autor: | Ilaria Iacobucci, Ashot S. Harutyunyan, Roland Jäger, Lisa Pieri, Tiina Berg, Paola Guglielmelli, Alessandro M. Vannucchi, Robert Kralovics, Klaudia Bagienski, Elisa Rumi, Daniela Pietra, Bettina Gisslinger, Giovanni Martinelli, Francesco Passamonti, Martin Schalling, Thorsten Klampfl, Heinz Gisslinger, Damla Olcaydu, Mario Cazzola |
|---|---|
| Přispěvatelé: | 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 AM, Gisslinger H, Kralovics R. |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Myeloid
Immunology Myeloproliferative neoplasm Polymorphism Single Nucleotide Biochemistry Leukemia Myeloid Chronic Atypical BCR-ABL Negative medicine Humans Point Mutation acute leukemia genome mutation Oligonucleotide Array Sequence Analysis Acute leukemia Myeloproliferative Disorders Janus kinase 2 biology Gene Expression Regulation Leukemic Myeloid leukemia Karyotype Cell Biology Hematology Janus Kinase 2 medicine.disease ETV6 Leukemia medicine.anatomical_structure Karyotyping Chronic Disease Disease Progression Cancer research biology.protein CHRONIC PHASE Genome-Wide Association Study |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|