Identification of CD105 (endoglin) as novel risk marker in CLL

Abstract

Several genetic and clinical markers are established as prognostic factors in chronic lymphocytic leukemia (CLL). However, additional markers are needed for risk stratification. Flow cytometric analysis is a mainstay of CLL diagnostics, thus identification of novel prognostic surface markers can improve risk assessment without increasing burden for patients and physicians. Furthermore, surface molecules preferentially expressed in high-risk cases could serve as therapeutic targets for immunotherapy. CD105 (endoglin) is a TGF-beta coreceptor and activates endothelial cells in healthy tissues and cancer. In addition, it is expressed on healthy hematopoietic precursors as well as lymphoid and myeloid leukemias. In acute myeloid leukemia (AML), a CD105 antibody is successfully applied in clinical studies. In CLL, mRNA expression of the CD105 gene ENG reportedly correlates with other risk factors but failed to show significant correlation with overall survival. However, CD105 protein expression in CLL has never been studied. We here analyzed CD105 surface expression on CLL cells from 71 patients by flow cytometry and report for the first time that substantial levels of CD105 are detectable on CLL cells in 70.4% of patients. Using receiver operating characteristics, we established a cutoff of 5.99% positive cells to distinguish between low and high CD105 levels, the latter correlating with decreased time to first treatment and overall survival. High CD105 expression further correlates with CD38 expression. Our study identified membrane expression of CD105 as a potential risk marker and therapeutic target in high-risk CLL. However, multivariant analyses of large cohorts should be performed in confirmatory studies.

Increased bleeding and thrombosis in myeloproliferative neoplasms mediated through altered expression of inherited platelet disorder genes

“…It is also an important regulator of the hematopoietic lineage. Expression of ENG has previously been noted in myelodysplastic syndromes, acute myeloid leukaemia, and chronic lymphocytic leukaemia [63][64][65] . Previous overexpression studies during embryoid body differentiation resulted in an increase of haemopoietic progenitors…”

Targeting CD38 in Neoplasms and Non-Cancer Diseases

“…CLL cells with unmutated IGHV genes expressed high levels of CD38, however, this association is not absolute and CD38 expression might vary during the disease course [ 104 , 105 ]. High expression of CD105 (endoglin) is predicted to be a potential risk marker, and the therapeutic target in high-risk CLL further correlates with CD38 expression [ 106 ].…”

Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles

“…Among these, endoglin, an auxiliary receptor of the transforming growth factor b (TGF-b) family, has emerged as a promising therapeutic target [3,4]. Endoglin (Eng; CD105) is a 180-kDa disulfide-linked homodimeric transmembrane glycoprotein [5,6] highly expressed by proliferating endothelial cells in tumor associated neoangiogenesis [7], as well as in a large number of cancers with poor prognosis [8][9][10][11][12][13]. The role of endoglin in tumor progression and metastasis has been studied in several cancer cell types using in vitro and in vivo models [14][15][16][17][18][19][20][21].…”