A single fusion signal for t(14;18)(q32;q21) translocation is present in both the follicular lymphoma and local endothelial cells

Abstract

Herein we reported a case of follicular lymphoma with 50.26% clonal malignant lymphocytes and 50% tumor cells positive for the immunoglobulin heavy chain gene and B-cell lymphoma 2 gene (IGH-BCL2). To determine whether endothelial cells (ECs) within the tumor share the feature of advanced malignancy, we isolated and purified the ECs from the tumor by using the immunomagnetic beads conjugated with a monoclonal antibody against CD34, a surface marker of ECs. Thereafter, we identified ECs according to their morphology and found that ECs presented consistently flat and elongated appearance with a lot of Weibel-Palade bodies in the cytoplasm. Results of flow cytometry confirmed that ECs isolated from the follicular lymphoma expressed high level of both vWF and CD34 and the purity of the ECs fraction was more than 90%. Additionally, we used FISH to check chromosomal aberration in the purified ECs and found that some of the ECs had only one fusion signal for the green IGH probe and the red BCL2 probe in contrast to typical t(14;18)(q32;q21) translocation with two fusion signals. This phenomenon was also observed in the tumor cells. It might be a different breakpoint of IGH in this case, which induced the loss of the fusion signal, indicating t(14;18)(q32;q21) translocation. The positive cells accounted for 18% of the isolated ECs from the tumor, indicating that a proportion of ECs from follicular lymphoma had the same chromosome aberration as the neoplastic cells.

Keywords

endothelial cells / follicular lymphoma / chromsome translocation / IGH-BCL2

References

[1] PapettiM., HermanI.M.. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol, 2002, 282(5): C947-C970

[2] KlagsbrunM., D’AmoreP.. Regulators of angiogenesis. Annu Rev Physiol, 1991, 53: 217-239

[3] KlagsbrunM., MosesM.A.. Molecular angiogenesis. Chem Biol, 1999, 6(8): R217-R224

[4] MosesM.A.. The regulation of neovascularization of matrix metalloproteinases and their inhibitors. Stem Cells, 1997, 15(3): 180-189

[5] HendrixM.J.C., SeftorE.A., HessA.R., et al.. Vasculogenic mimicry and tumor-cell plasticity: lessons from melanoma. Nat Rev Cancer, 2003, 3(6): 411-421

[6] CrosbyJ.R., KaminskiW.E., SchattemanG., et al.. Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ Res, 2000, 87(9): 728-730

[7] UrbichC., DimmelerS.. Endothelial progenitor cells: characterization and role in vascular biology. Cir Res, 2004, 95(4): 343-353

[8] ChangY.S., di TomasoE., McDonaldD.M., et al.. Mosaic blood vessels in tumors:frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci USA, 2000, 97(26): 14608-14613

[9] HidaK., HidaY., AminD.N., et al.. Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res, 2004, 64(22): 8249-8255

[10] StreubelB., ChottA., HuberD., et al.. Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas. N Engl J Med, 2004, 351(3): 250-259

[11] van BeijnumJ.R., RouschM., CastermansK., et al.. Isolation of endothelial cells from fresh tissues. Nat Protoc, 2008, 3(6): 1085-1091

[12] OkruhlicováL., DlugosováK., MitasíkováM., et al.. Ultrastructural characteristics of aortic endothelial cells in borderline hypertensive rats exposed to chronic social stress. Physiol Res, 2008, 57(Suppl2): S31-S37

[13] PusztaszeriM.P., SeelentagW., BosmanF.T.. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem, 2006, 54(4): 385-395

[14] StreubelB., LamprechtA., DierlammJ., et al.. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood, 2003, 101(6): 2335-2339

[15] LydenD., HattoriK., DiasS., et al.. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med, 2001, 7(11): 1194-1201

[16] GunsiliusE.. Evidence from a leukemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Adv Exp Med Biol, 2003, 522: 17-24

[17] KerbelR.S.. Clinical trials of antiangiogenic drugs: opportunities, problems, and assessment of initial results. J Clin Oncol, 2001, 19(18Suppl): 45S-51S