TY - JOUR
T1 - Absence of tissue factor is characteristic of lymphoid malignancies of both T- and B-cell origin
AU - Cesarman-Maus, Gabriela
AU - Braggio, Esteban
AU - Lome-Maldonado, Carmen
AU - Morales-Leyte, Ana Lilia
AU - Fonseca, Rafael
N1 - Funding Information:
Sources disclosure: Rafael Fonseca is a Clinical Investigator of the Damon Runyon Cancer Research Fund. This work is supported by grants SPORE CA90297052, P01 CA62242, R01 CA83724, ECOG CA 21115T, Predolin Foundation, Mayo Clinic Cancer Center and the Mayo Foundation.
Funding Information:
The authors would like to acknowledge the Broad Institute, and the Novartis Institutes for Biomedical Research for making available the genomics data of The Cancer Cell Line Encyclopedia (CCLE) project. E.B. is a recipient of the Marriott Specialized Workforce Development Awards in Individualized Medicine, The Henry Predolin Foundation Career Development Award and the George Haub Family Career Development Award Fund in Cancer Research. We thank Mrs. Lara Karchmar M.A., Ed for proofreading of the manuscript.
PY - 2014/4
Y1 - 2014/4
N2 - Background Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias. Objectives We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression. Methods We analyzed TF gene (F3) expression in lymphoid (N = 114), myeloid (N = 49) and solid tumor (N = 856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC). Results In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11). Conclusions We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor.
AB - Background Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias. Objectives We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression. Methods We analyzed TF gene (F3) expression in lymphoid (N = 114), myeloid (N = 49) and solid tumor (N = 856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC). Results In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11). Conclusions We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor.
KW - Cancer
KW - Hematological malignancies
KW - Leukemias
KW - Lymphomas
KW - Tissue factor
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U2 - 10.1016/j.thromres.2014.01.020
DO - 10.1016/j.thromres.2014.01.020
M3 - Article
C2 - 24491425
AN - SCOPUS:84896129265
SN - 0049-3848
VL - 133
SP - 606
EP - 609
JO - Thrombosis research
JF - Thrombosis research
IS - 4
ER -