{"entity": "researcher", "timestamp": "2026-06-08T05:03:53.414Z", "family": "J\u00f6nsson", "given": "Jan-Ingvar", "initials": "JI", "orcid": "0000-0003-4814-978X", "affiliations": ["Experimental Hematology Unit, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/fcc87190783c48229913c2a35a2782c8.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/fcc87190783c48229913c2a35a2782c8"}}, "publications": [{"entity": "publication", "iuid": "49429afd445b4071bb75a310e829b590", "links": {"self": {"href": "https://publications.scilifelab.se/publication/49429afd445b4071bb75a310e829b590.json"}, "display": {"href": "https://publications.scilifelab.se/publication/49429afd445b4071bb75a310e829b590"}}, "title": "Multiplexed single\u2010cell mass cytometry reveals distinct inhibitory effects on intracellular phosphoproteins by midostaurin in combination with chemotherapy in AML cells", "authors": [{"family": "R\u00f6rby", "given": "Emma", "initials": "E", "orcid": "0000-0002-4816-0391", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d68bac501964ad2827833fe712c3ee4.json"}}, {"family": "Adolfsson", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Hultin", "given": "Erik", "initials": "E"}, {"family": "Gustafsson", "given": "Thomas", "initials": "T"}, {"family": "Lotfi", "given": "Kourosh", "initials": "K"}, {"family": "Cammenga", "given": "J\u00f6rg", "initials": "J"}, {"family": "J\u00f6nsson", "given": "Jan Ingvar", "initials": "JI", "orcid": "0000-0003-4814-978X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcc87190783c48229913c2a35a2782c8.json"}}], "type": "journal-article", "published": "2021-12-00", "journal": {"title": "Exp Hematol Oncol", "issn": "2162-3619", "volume": "10", "issue": "1", "pages": "7", "issn-l": null}, "abstract": "Fms-related tyrosine kinase 3 (FLT3) receptor serves as a prognostic marker and therapeutic target in acute myeloid leukemia (AML). Approximately one-third of AML patients carry mutation in FLT3, associated with unfavourable prognosis and high relapse rate. The multitargeted kinase inhibitor midostaurin (PKC412) in combination with standard chemotherapy (daunorubicin and cytarabine) was recently shown to increase overall survival of AML patients. For that reason, PKC412 has been approved for treatment of AML patients with FLT3-mutation. PKC412 synergizes with standard chemotherapy, but the mechanism involved is not fully understood and the risk of relapse is still highly problematic.\n\nBy utilizing the unique nature of mass cytometry for single cell multiparameter analysis, we have explored the proteomic effect and intracellular signaling response in individual leukemic cells with internal tandem duplication of FLT3 (FLT3-ITD) after midostaurin treatment in combination with daunorubicin or cytarabine.\n\nWe have identified a synergistic inhibition of intracellular signaling proteins after PKC412 treatment in combination with daunorubicin. In contrast, cytarabine antagonized phosphorylation inhibition of PKC412. Moreover, we found elevated levels of FLT3 surface expression after cytarabine treatment. Interestingly, the surface localization of FLT3 receptor increased in vivo on the blast cell population of two AML patients during day 3 of induction therapy (daunorubicin; once/day from day 1-3 and cytarabine; twice/day from day 1-7). We found FLT3 receptor expression to correlate with intracellular cytarabine (AraC) response. AML cell line cultured with AraC with or without PKC412 had an antagonizing phosphorylation inhibition of pAKT (p = 0.042 and 0.0261, respectively) and pERK1/2 (0.0134 and 0.0096, respectively) in FLT3high compared to FLT3low expressing cell populations.\n\nOur study provides insights into how conventional chemotherapy affects protein phosphorylation of vital signaling proteins in human leukemia cells. The results presented here support further investigation of novel strategies to treat FLT3-mutated AML patients with PKC412 in combination with chemotherapy agents and the potential development of novel treatment strategies.", "doi": "10.1186/s40164-021-00201-w", "pmid": "33531064", "labels": {"Cellular Immunomonitoring": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7852110"}, {"db": "pii", "key": "10.1186/s40164-021-00201-w"}], "notes": [], "created": "2021-02-15T11:34:55.547Z", "modified": "2023-06-19T07:54:13.846Z"}, {"entity": "publication", "iuid": "95e3397aa97f499691827ab1770b0047", "links": {"self": {"href": "https://publications.scilifelab.se/publication/95e3397aa97f499691827ab1770b0047.json"}, "display": {"href": "https://publications.scilifelab.se/publication/95e3397aa97f499691827ab1770b0047"}}, "title": "The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer.", "authors": [{"family": "Liu", "given": "Na", "initials": "N"}, {"family": "Cui", "given": "Weiyingqi", "initials": "W"}, {"family": "Jiang", "given": "Xia", "initials": "X"}, {"family": "Zhang", "given": "Zhiyong", "initials": "Z"}, {"family": "Gnosa", "given": "Sebastian", "initials": "S"}, {"family": "Ali", "given": "Zaheer", "initials": "Z"}, {"family": "Jensen", "given": "Lasse", "initials": "L"}, {"family": "J\u00f6nsson", "given": "Jan-Ingvar", "initials": "JI", "orcid": "0000-0003-4814-978X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcc87190783c48229913c2a35a2782c8.json"}}, {"family": "Blockhuys", "given": "St\u00e9phanie", "initials": "S"}, {"family": "Lam", "given": "Eric W-F", "initials": "EW"}, {"family": "Zhao", "given": "Zengren", "initials": "Z"}, {"family": "Ping", "given": "Jie", "initials": "J"}, {"family": "Xie", "given": "Ning", "initials": "N"}, {"family": "Kopsida", "given": "Maria", "initials": "M"}, {"family": "Wang", "given": "Xin", "initials": "X"}, {"family": "Sun", "given": "Xiao-Feng", "initials": "XF"}], "type": "journal article", "published": "2019-08-01", "journal": {"title": "Int. J. Radiat. Oncol. Biol. Phys.", "issn": "1879-355X", "volume": "104", "issue": "5", "pages": "1153-1164", "issn-l": "0360-3016"}, "abstract": "To explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.\n\nRho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was used to detect RhoB downstream signaling factors. RhoB and Forkhead box M1 (FOXM1) expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiation therapy trial.\n\nRhoB expression was related to radiation resistance. Complete depletion of the RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish models. Probing signaling using mass cytometry-based single-cell analysis showed that the Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells, and the inhibition of FOXM1 led to lower survival rates and attenuated migration and invasion abilities of the cells after radiation. In the patients who underwent radiation therapy, RhoB overexpression was related to high FOXM1, late Tumor, Node, Metastasis stage, high distant recurrence, and poor survival independent of other clinical factors.\n\nRhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.", "doi": "10.1016/j.ijrobp.2019.04.021", "pmid": "31039421", "labels": {"Cellular Immunomonitoring": "Service"}, "xrefs": [{"db": "pii", "key": "S0360-3016(19)30653-4"}], "notes": [], "created": "2019-12-02T12:43:37.113Z", "modified": "2021-07-08T09:31:31.587Z"}, {"entity": "publication", "iuid": "f2b37f297e674bd59ee4fa8b88976193", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f2b37f297e674bd59ee4fa8b88976193.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f2b37f297e674bd59ee4fa8b88976193"}}, "title": "miR-20b regulates expression of proteinase-activated receptor-1 (PAR-1) thrombin receptor in melanoma cells.", "authors": [{"family": "Saleiban", "given": "Amina", "initials": "A"}, {"family": "Fax\u00e4lv", "given": "Lars", "initials": "L"}, {"family": "Claesson", "given": "Kjersti", "initials": "K"}, {"family": "J\u00f6nsson", "given": "Jan-Ingvar", "initials": "JI", "orcid": "0000-0003-4814-978X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcc87190783c48229913c2a35a2782c8.json"}}, {"family": "Osman", "given": "Abdimajid", "initials": "A"}], "type": "journal article", "published": "2014-05-00", "journal": {"volume": "27", "issn": "1755-148X", "issue": "3", "pages": "431-441", "title": "Pigment Cell Melanoma Res", "issn-l": "1755-1471"}, "abstract": "The proteinase-activated receptor 1 (PAR-1) plays a central role in melanoma progression and its expression level is believed to correlate with the degree of cancer invasiveness. Here, we show that PAR-1 is post-transcriptionally regulated by miR-20b microRNA in human melanoma cells. PAR-1 was found to be expressed in metastatic melanoma cells but was barely detectable in primary melanoma. By transducing primary melanoma cells with a lentivirus containing a 3'-UTR construct of PAR-1 mRNA, we could show that endogenous melanoma microRNAs interacted with PAR-1 3'-UTR and silenced a fused luciferase reporter. Transfection of an inhibitor against miR-20b into primary melanoma cells reversed this process. Finally, transfection of miR-20b mimic into metastatic melanoma cells caused downregulation of the luciferase reporter. We conclude that miR-20b regulates expression of melanoma PAR-1 receptor, which may explain the differential expression of PAR-1 observed in human melanoma.", "doi": "10.1111/pcmr.12217", "pmid": "24405508", "labels": {"Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics (NBIS)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:56:34.377Z", "modified": "2021-07-08T09:31:31.596Z"}]}