{"entity": "researcher", "timestamp": "2026-08-26T22:47:26.334Z", "family": "Stetka", "given": "J", "initials": "J", "orcid": "0000-0003-4301-2856", "affiliations": ["Department of Biology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef1e30ff8c9f47efa1bf5e4454281b90.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef1e30ff8c9f47efa1bf5e4454281b90"}}, "publications": [{"entity": "publication", "iuid": "3103bb8dba2445ee8caddd9b4ba66fba", "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"}, {"entity": "publication", "iuid": "1bf7084a70bd4d28b96b43088ce659e7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1bf7084a70bd4d28b96b43088ce659e7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1bf7084a70bd4d28b96b43088ce659e7"}}, "title": "Addiction to DUSP1 protects JAK2V617F-driven polycythemia vera progenitors against inflammatory stress and DNA damage, allowing chronic proliferation.", "authors": [{"family": "Stetka", "given": "J", "initials": "J", "orcid": "0000-0003-4301-2856", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef1e30ff8c9f47efa1bf5e4454281b90.json"}}, {"family": "Vyhlidalova", "given": "P", "initials": "P", "orcid": "0000-0002-2522-6749", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e6c2c42653c418bb27a01e32fbe9eb4.json"}}, {"family": "Lanikova", "given": "L", "initials": "L"}, {"family": "Koralkova", "given": "P", "initials": "P"}, {"family": "Gursky", "given": "J", "initials": "J", "orcid": "0000-0002-5761-7066", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6c2eb2724144401b00a5b0c21fbfa38.json"}}, {"family": "Hlusi", "given": "A", "initials": "A"}, {"family": "Flodr", "given": "P", "initials": "P"}, {"family": "Hubackova", "given": "S", "initials": "S"}, {"family": "Bartek", "given": "J", "initials": "J"}, {"family": "Hodny", "given": "Z", "initials": "Z"}, {"family": "Divoky", "given": "V", "initials": "V"}], "type": "journal article", "published": "2019-07-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "38", "issue": "28", "pages": "5627-5642", "issn-l": "0950-9232"}, "abstract": "Inflammatory and oncogenic signaling converge in disease evolution of BCR-ABL-negative myeloproliferative neoplasms, clonal hematopoietic stem cell disorders characterized by gain-of-function mutation in JAK2 kinase (JAK2V617F), with highest prevalence in patients with polycythemia vera (PV). Despite the high risk, DNA-damaging inflammatory microenvironment, PV progenitors tend to preserve their genomic stability over decades until their progression to post-PV myelofibrosis/acute myeloid leukemia. Using induced pluripotent stem cells-derived CD34+ progenitor-enriched cultures from JAK2V617F+ PV patient and from JAK2 wild-type healthy control, CRISPR-modified HEL cells and patients' bone marrow sections from different disease stages, we demonstrate that JAK2V617F induces an intrinsic IFN\u03b3- and NF-\u03baB-associated inflammatory program, while suppressing inflammation-evoked DNA damage both in vitro and in vivo. We show that cells with JAK2V617F tightly regulate levels of inflammatory cytokines-induced reactive oxygen species, do not fully activate the ATM/p53/p21waf1 checkpoint and p38/JNK MAPK stress pathway signaling when exposed to inflammatory cytokines, suppress DNA single-strand break repair genes' expression yet overexpress the dual-specificity phosphatase (DUSP) 1. RNAi-mediated knock-down and pharmacological inhibition of DUSP1, involved in p38/JNK deactivation, in HEL cells reveals growth addiction to DUSP1, consistent with enhanced DNA damage response and apoptosis in DUSP1-inhibited parental JAK2V617F+ cells, but not in CRISPR-modified JAK2 wild-type cells. Our results indicate that the JAK2V617F+ PV progenitors utilize DUSP1 activity as a protection mechanism against DNA damage accumulation, promoting their proliferation and survival in the inflammatory microenvironment, identifying DUSP1 as a potential therapeutic target in PV.", "doi": "10.1038/s41388-019-0813-7", "pmid": "30967632", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6756199"}, {"db": "pii", "key": "10.1038/s41388-019-0813-7"}], "notes": [], "created": "2026-08-20T08:48:15.442Z", "modified": "2026-08-20T08:48:15.631Z"}]}