{"entity": "publication", "iuid": "3103bb8dba2445ee8caddd9b4ba66fba", "timestamp": "2026-08-26T22:47:26.042Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3103bb8dba2445ee8caddd9b4ba66fba.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3103bb8dba2445ee8caddd9b4ba66fba"}}, "title": "Role of DNA Damage Response in Suppressing Malignant Progression of Chronic Myeloid Leukemia and Polycythemia Vera: Impact of Different Oncogenes.", "authors": [{"family": "Stetka", "given": "Jan", "initials": "J", "orcid": "0000-0003-4301-2856", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef1e30ff8c9f47efa1bf5e4454281b90.json"}}, {"family": "Gursky", "given": "Jan", "initials": "J"}, {"family": "Li\u00f1an Velasquez", "given": "Julie", "initials": "J"}, {"family": "Mojzikova", "given": "Renata", "initials": "R"}, {"family": "Vyhlidalova", "given": "Pavla", "initials": "P", "orcid": "0000-0002-2522-6749", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e6c2c42653c418bb27a01e32fbe9eb4.json"}}, {"family": "Vrablova", "given": "Lucia", "initials": "L"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Divoky", "given": "Vladimir", "initials": "V", "orcid": "0000-0003-0202-245X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/66584f6fcbb848e9b3052748a6c220d9.json"}}], "type": "journal article", "published": "2020-04-07", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "12", "issue": "4", "issn-l": "2072-6694"}, "abstract": "Inflammatory and oncogenic signaling, both known to challenge genome stability, are key drivers of BCR-ABL-positive chronic myeloid leukemia (CML) and JAK2 V617F-positive chronic myeloproliferative neoplasms (MPNs). Despite similarities in chronic inflammation and oncogene signaling, major differences in disease course exist. Although BCR-ABL has robust transformation potential, JAK2 V617F-positive polycythemia vera (PV) is characterized by a long and stable latent phase. These differences reflect increased genomic instability of BCR-ABL-positive CML, compared to genome-stable PV with rare cytogenetic abnormalities. Recent studies have implicated BCR-ABL in the development of a \"mutator\" phenotype fueled by high oxidative damage, deficiencies of DNA repair, and defective ATR-Chk1-dependent genome surveillance, providing a fertile ground for variants compromising the ATM-Chk2-p53 axis protecting chronic phase CML from blast crisis. Conversely, PV cells possess multiple JAK2 V617F-dependent protective mechanisms, which ameliorate replication stress, inflammation-mediated oxidative stress and stress-activated protein kinase signaling, all through up-regulation of RECQL5 helicase, reactive oxygen species buffering system, and DUSP1 actions. These attenuators of genome instability then protect myeloproliferative progenitors from DNA damage and create a barrier preventing cellular stress-associated myelofibrosis. Therefore, a better understanding of BCR-ABL and JAK2 V617F roles in the DNA damage response and disease pathophysiology can help to identify potential dependencies exploitable for therapeutic interventions.", "doi": "10.3390/cancers12040903", "pmid": "32272770", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7226398"}, {"db": "pii", "key": "cancers12040903"}], "notes": [], "created": "2026-08-20T13:39:18.052Z", "modified": "2026-08-20T13:39:18.173Z"}