title: Expression of circulating miRNAs associated with lymphocyte differentiation and activation in CLL-another piece in the puzzle.
abstract: Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes. Results were analyzed regarding the most important prognostic factors. We have found that the general expression of examined miRNAs in CLL patients was lower as compared to healthy volunteers. Only miR-34a-5p, miR31-5p, miR-155-5p, miR-150-5p, miR-15a-3p, and miR-29a-3p were expressed on a higher level. Alterations of expression observed in CLL patients involved miRNAs associated both with B and T lymphocyte differentiation and activation. The most important discriminating factors for all functional miRNA groups were trisomy 12, CD38 expression, B2M level, WBC, and NOTCH1 gene mutation. Correlation of expression of miRNAs related to T lymphocytes with prognostic factors proves their supportive function in a leukemic microenvironment. Further studies utilizing a larger test group of patients may warrant the identification of circulating miRNAs that are key players in intercellular interactions and should be considered in the design of microenvironment-targeted therapies.
authors.affiliation: Department of Cancer Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland. aafilip@hotmail.com.
authors.forename: Agata A
authors.initials: AA
authors.lastname: Filip
authors.affiliation: Department of Cancer Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Grenda
authors.affiliation: Department of Cancer Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Popek
authors.affiliation: Department of Cancer Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Koczkodaj
authors.affiliation: Department of Cancer Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Michalak-Wojnowska
authors.affiliation: Department of Cancer Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Budzyński
authors.affiliation: Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wąsik-Szczepanek
authors.affiliation: Department of Cancer Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Zmorzyński
authors.affiliation: Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Karczmarczyk
authors.affiliation: Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Giannopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D035683:MicroRNAs
keywords: CLL; Circulating miRNA; Lymphocyte differentiation; Microenvironment; Prognostic factors