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Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles

  • Authors:
    • Håkon Reikvam
    • Anita Ryningen
    • Lars Rune Sæterdal
    • Ina  Nepstad
    • Brynjar Foss
    • Øystein Bruserud
  • View Affiliations / Copyright

    Affiliations: Institute of Clinical Science, University of Bergen, Bergen, Norway, Department of Health Studies, University of Stavanger, Stravanger, Norway
    Copyright: © Reikvam et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 645-652
    |
    Published online on: December 19, 2014
       https://doi.org/10.3892/ijmm.2014.2045
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Abstract

Bone marrow stromal cells support both normal and malignant hematopoiesis. Τhis support is mediated through the local cytokine network and by direct cell‑cell interactions mediated via adhesion molecules and the formation of gap junctions by connexins. Previous studies on connexins in human acute myeloid leukemia (AML) have mainly focused on the investigation of leukemia cell lines. In the present study, we therefore investigated the expression of various connexins at the protein (i.e., cell surface expression) and mRNA level in primary human AML cells. The cell surface expression of the connexins, Cx26, Cx32, Cx37, Cx43 and Cx45, varied considerably between patients, and detectable levels were observed only for subsets of patients. On the whole, Cx43 and Cx45 showed the highest cell surface expression. Connexin expression was dependent on AML cell differentiation, but showed no association with cytogenetic abnormalities or mutations of the fms-related tyrosine kinase 3 (FLT3) or nucleophosmin (NPM)‑1 genes. By contrast, only Cx45 showed a significant variation between patients at the mRNA level. A high Cx45 expression was associated with the altered regulation of the mitogen‑activated protein kinase (MAPK) pathway and the release of pro-inflammatory cytokines [interleukin (IL)‑17, tumor necrosis factor (TNF), interferon‑γ], whereas a low Cx45 expression was associated with the altered regulation of protein functions (i.e., ligase activity, protein folding and catabolism). There was no significant correlation observed between the connexin mRNA and protein levels. Thus, differences in connexin expression can be used to subclassify AML patients. Differences in connexin cell surface expression profiles are not reflected at the mRNA level and have to be directly examined, whereas variations in Cx45 mRNA expression are associated with differences in cell signaling and the regulation of protein functions.
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1 

Shiozawa Y, Havens AM, Pienta KJ and Taichman RS: The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites. Leukemia. 22:941–950. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Foss B, Hervig T and Bruserud Ø: Connexins are active participants of hematopoietic stem cell regulation. Stem Cells Dev. 18:807–812. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Shipley JL and Butera JN: Acute myelogenous leukemia. Exper Hematol. 37:649–658. 2009. View Article : Google Scholar

4 

Foss B, Ulvestad E and Bruserud Ø: Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts. Eur J Haematol. 66:365–376. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Bruserud Ø: IL-4, IL-10 and IL-13 in acute myelogenous leukemia. Cytokines Cell Mol Ther. 4:187–198. 1998.PubMed/NCBI

6 

Foss B, Mentzoni L and Bruserud Ø: Effects of vascular endothelial growth factor on acute myelogenous leukemia blasts. J Hematother Stem Cell Res. 10:81–93. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Ryningen A, Wergeland L, Glenjen N, Gjertsen BT and Bruserud Ø: In vitro crosstalk between fibroblasts and native human acute myelogenous leukemia (AML) blasts via local cytokine networks results in increased proliferation and decreased apoptosis of AML cells as well as increased levels of proangiogenic Interleukin 8. Leuk Res. 29:185–196. 2005. View Article : Google Scholar

8 

Hatfield K, Ryningen A, Corbascio M and Bruserud Ø: Microvascular endothelial cells increase proliferation and inhibit apoptosis of native human acute myelogenous leukemia blasts. Int J Cancer. 119:2313–2321. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Bruserud Ø, Ryningen A, Wergeland L, Glenjen NI and Gjertsen BT: Osteoblasts increase proliferation and release of proangiogenic interleukin 8 by native human acute myelogenous leukemia blasts. Haematologica. 89:391–402. 2004.PubMed/NCBI

10 

Konopleva M, Konoplev S, Hu W, Zaritskey AY, Afanasiev BV and Andreeff M: Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia. 16:1713–1724. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Foss B, Tronstad KJ and Bruserud Ø: Connexin-based signaling in acute myelogenous leukemia (AML). Biochim Biophys Acta. 1798:1–8. 2010. View Article : Google Scholar

12 

Weber MC and Tykocinski ML: Bone marrow stromal cell blockade of human leukemic cell differentiation. Blood. 83:2221–2229. 1994.PubMed/NCBI

13 

Paraguassú-Braga FH, Borojevic R, Bouzas LF, Barcinski MA and Bonomo A: Bone marrow stroma inhibits proliferation and apoptosis in leukemic cells through gap junction-mediated cell communication. Cell Death Differ. 10:1101–1108. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Li X, Xu Y-B, Wang Q, et al: Leukemogenic AML1-ETO fusion protein upregulates expression of connexin 43: the role in AML1-ETO-induced growth arrest in leukemic cells. J Cell Physiol. 208:594–601. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Krenacs T and Rosendaal M: Connexin43 gap junctions in normal, regenerating, and cultured mouse bone marrow and in human leukemias: their possible involvement in blood formation. Am J Pathol. 152:993–1004. 1998.PubMed/NCBI

16 

Yi S, Chen Y, Wen L, Yang L and Cui G: Expression of connexin 32 and connexin 43 in acute myeloid leukemia and their roles in proliferation. Oncol Lett. 4:1003–1007. 2012.PubMed/NCBI

17 

Liu Y, Zhang X, Li ZJ and Chen XH: Up-regulation of Cx43 expression and GJIC function in acute leukemia bone marrow stromal cells post-chemotherapy. Leuk Res. 34:631–640. 2010. View Article : Google Scholar

18 

Bruserud Ø, Hovland R, Wergeland L, Huang TS and Gjertsen BT: Flt3-mediated signaling in human acute myelogenous leukemia (AML) blasts: a functional characterization of Flt3-ligand effects in AML cell populations with and without genetic Flt3 abnormalities. Haematologica. 88:416–428. 2003.PubMed/NCBI

19 

Hatfield KJ, Hovland R, Øyan AM, et al: Release of angio-poietin-1 by primary human acute myelogenous leukemia cells is associated with mutations of nucleophosmin, increased by bone marrow stromal cells and possibly antagonized by high systemic angiopoietin-2 levels. Leukemia. 22:287–293. 2008. View Article : Google Scholar

20 

Tsykunova G, Reikvam H, Hovland R and Bruserud Ø: The surface molecule signature of primary human acute myeloid leukemia (AML) cells is highly associated with NPM1 mutation status. Leukemia. 26:557–559. 2012. View Article : Google Scholar

21 

Bruserud Ø: Effect of dipyridamole, theophyllamine and verapamil on spontaneous in vitro proliferation of myelogenous leukaemia cells. Acta Oncol. 31:53–58. 1992. View Article : Google Scholar : PubMed/NCBI

22 

Dysvik B and Jonassen I: J-Express: exploring gene expression data using Java. Bioinformatics. 17:369–370. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Stavrum AK, Petersen K, Jonassen I and Dysvik B: Analysis of gene-expression data using J-Express. Curr Protoc Bioinformatics. Chapter 7: Unit 7.3. 2008. View Article : Google Scholar : PubMed/NCBI

24 

VanSlyke JK and Musil LS: Cytosolic stress reduces degradation of connexin43 internalized from the cell surface and enhances gap junction formation and function. Mol Biol Cell. 16:5247–5257. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Hirabayashi Y, Yoon BI, Tsuboi I, et al: Protective role of connexin 32 in steady-state hematopoiesis, regeneration state, and leukemogenesis. Exp Biol Med. 232:700–712. 2007.

26 

Döhner H, Estey EH, Amadori S, et al: Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 115:453–474. 2010. View Article : Google Scholar

27 

Dürig J, Rosenthal C, Halfmeyer K, et al: Intercellular communication between bone marrow stromal cells and CD34+ haematopoietic progenitor cells is mediated by connexin 43-type gap junctions. Br J Haematol. 111:416–425. 2000. View Article : Google Scholar

28 

Montecino-Rodriguez E, Leathers H and Dorshkind K: Expression of connexin 43 (Cx43) is critical for normal hematopoiesis. Blood. 96:917–924. 2000.PubMed/NCBI

29 

Presley CA, Lee AW, Kastl B, et al: Bone marrow connexin-43 expression is critical for hematopoietic regeneration after chemotherapy. Cell Commun Adhes. 12:307–317. 2005. View Article : Google Scholar

30 

Wong RC, Pébay A, Nguyen LT, Koh KL and Pera MF: Presence of functional gap junctions in human embryonic stem cells. Stem Cells. 22:883–889. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Huettner JE, Lu A, Qu Y, Wu Y, Kim M and McDonald JW: Gap junctions and connexon hemichannels in human embryonic stem cells. Stem Cells. 24:1654–1667. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Wörsdörfer P, Maxeiner S, Markopoulos C, et al: Connexin expression and functional analysis of gap junctional communication in mouse embryonic stem cells. Stem Cells. 26:431–439. 2008. View Article : Google Scholar

33 

Wong CW, Christen T, Roth I, et al: Connexin37 protects against atherosclerosis by regulating monocyte adhesion. Nat Med. 12:950–954. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Reikvam H, Ryningen A, Sæterdal LR, Nepstad I, Foss B and Bruserud Ø: Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles. Int J Mol Med 35: 645-652, 2015.
APA
Reikvam, H., Ryningen, A., Sæterdal, L.R., Nepstad, I., Foss, B., & Bruserud, Ø. (2015). Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles. International Journal of Molecular Medicine, 35, 645-652. https://doi.org/10.3892/ijmm.2014.2045
MLA
Reikvam, H., Ryningen, A., Sæterdal, L. R., Nepstad, I., Foss, B., Bruserud, Ø."Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles". International Journal of Molecular Medicine 35.3 (2015): 645-652.
Chicago
Reikvam, H., Ryningen, A., Sæterdal, L. R., Nepstad, I., Foss, B., Bruserud, Ø."Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles". International Journal of Molecular Medicine 35, no. 3 (2015): 645-652. https://doi.org/10.3892/ijmm.2014.2045
Copy and paste a formatted citation
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Spandidos Publications style
Reikvam H, Ryningen A, Sæterdal LR, Nepstad I, Foss B and Bruserud Ø: Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles. Int J Mol Med 35: 645-652, 2015.
APA
Reikvam, H., Ryningen, A., Sæterdal, L.R., Nepstad, I., Foss, B., & Bruserud, Ø. (2015). Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles. International Journal of Molecular Medicine, 35, 645-652. https://doi.org/10.3892/ijmm.2014.2045
MLA
Reikvam, H., Ryningen, A., Sæterdal, L. R., Nepstad, I., Foss, B., Bruserud, Ø."Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles". International Journal of Molecular Medicine 35.3 (2015): 645-652.
Chicago
Reikvam, H., Ryningen, A., Sæterdal, L. R., Nepstad, I., Foss, B., Bruserud, Ø."Connexin expression in human acute myeloid leukemia cells: Identification of patient subsets based on protein and global gene expression profiles". International Journal of Molecular Medicine 35, no. 3 (2015): 645-652. https://doi.org/10.3892/ijmm.2014.2045
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