The roles of autocrine and paracrine IL-6 in Plasma Cell Neoplasia

Plasma cell neoplasms (PCN) account for one percent of all cancers, and are the second most common blood cancer in the United States. Research in the Janz laboratory focuses on the role of Myc, a potent oncogene, in the formation of PCN. Previous work has demonstrated that IL-6 is necessary for PCN development and that aberrant IL-6 production accelerates PCN formation. My project is aimed at determining the relative importance of autocrine and paracrine IL-6 in PCN formation. In addition, I am interested in determining the role of IL-6 trans signaling in PCN development. These studies will identify the contributions of IL-6 production by premalignant B cells and stromal cells in mediating PCN formation. This work will lead to a better understanding of the relationship between premalignant B cells and their stroma, and the effects of this interplay on the development of PCN.

Tompkins VS, Rosean TR, Holman CJ, DeHoedt C, Olivier AK, Duncan KM, Jing X, Foor SD, Acevedo MR, Walsh SA, Tricot G, Zhan F, Janz S. Adoptive B-cell transfer mouse model of human myeloma. Leukemia. 2016 Apr;30(4):962-6. doi:10.1038/leu.2015.197. PubMed PMID: 26202932; PubMed Central PMCID: PMC4821809.

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Tompkins VS, Sompallae R, Rosean TR, Walsh S, Acevedo M, Kovalchuk AL, Han SS, Jing X, Holman C, Rehg JE, Herms S, Sunderland JS, Morse HC, Janz S. Transgenic mouse model of IgM(+) lymphoproliferative disease mimicking Waldenström macroglobulinemia. Blood Cancer J. 2016 Nov 4;6(11):e488. doi:10.1038/bcj.2016.95. PubMed PMID: 27813533; PubMed Central PMCID: PMC5148059.

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Reed SM, Hagen J, Muniz VP, Rosean TR, Borcherding N, Sciegienka S, Goeken JA, Naumann PW, Zhang W, Tompkins VS, Janz S, Meyerholz DK, Quelle DE. NIAM-deficient mice are predisposed to the development of proliferative lesions including B-cell lymphomas. PLoS One. 2014 Nov 13;9(11):e112126. doi:10.1371/journal.pone.0112126. eCollection 2014. PubMed PMID: 25393878; PubMed Central PMCID: PMC4231569.

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Norian LA, Kresowik TP, Rosevear HM, James BR, Rosean TR, Lightfoot AJ, Kucaka TA, Schwarz C, Weydert CJ, Henry MD, Griffith TS. Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF-related apoptosis-inducing ligand (TRAIL)/CpG immunotherapy. PLoS One. 7(2):e31085. 2012.

Duncan K, Rosean TR, Tompkins VS, Olivier A, Sompallae R, Zhan F, Tricot G, Acevedo MR, Ponto LL, Walsh SA, Tygrett LT, Berger AJ, Waldschmidt T, Morse HC 3rd, Sunderland JJ, Janz S. (18)F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib. Blood Cancer J. 2013 Nov 29;3:e165. doi: 10.1038/bcj.2013.61. PubMed PMID:24292417; PubMed Central PMCID: PMC3880444.

Ballas ZK, Buchta CM, Rosean TR, Heusel JW, Shey MR. Role of NK cell subsets in organ-specific murine melanoma metastasis. PLoS One. 2013 Jun 11;8(6):e65599. doi: 10.1371/journal.pone.0065599. Print 2013. PubMed PMID: 23776508; PubMed Central PMCID: PMC3679158.