Abstract

While several genetic and morphological markers are established and serve to guide therapy of acute myeloid leukaemia (AML), there is still profound need to identify additional markers to better stratify patients. CD105 (Endoglin) is a type I transmembrane protein reported to induce activation and proliferation of endothelial cells. In addition, CD105 is expressed in haematological malignancies and the vessels of solid tumours. Here, CD105 associates with unfavourable disease course, but so far no data are available on the prognostic relevance of CD105 in haematological malignancies. We here generated a novel CD105 antibody for analysis of expression and prognostic relevance of CD105 in a cohort of 62 AML patients. Flow cytometric analysis revealed substantial expression in the various AML FAB types, with FAB M3 type displaying significantly lower surface levels. Next we established a cut-off specific fluorescence level of 5.22 using receiver-operating characteristics, which allowed to group patients in cases with CD105lo and CD105hi surface expression and revealed that high CD105 expression correlated significantly with poor overall and progression free survival. In conclusion, we here identify CD105 expression as a novel prognostic marker in AML, which may serve to optimize follow up and treatment decisions for AML patients.

Highlights

  • While several genetic and morphological markers are established and serve to guide therapy of acute myeloid leukaemia (AML), there is still profound need to identify additional markers to better stratify patients

  • CD105 expression has been described in myelodysplastic syndrome (MDS), acute lymphoblastic leukaemia (ALL) and AML21–23, but its prognostic relevance in these and other haematopoietic malignancies has not been assessed so far

  • The transforming growth factor (TGF)-beta co-receptor CD105 plays a major role in foetal, adult and malignant angiogenesis

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Summary

Introduction

While several genetic and morphological markers are established and serve to guide therapy of acute myeloid leukaemia (AML), there is still profound need to identify additional markers to better stratify patients. We here generated a novel CD105 antibody for analysis of expression and prognostic relevance of CD105 in a cohort of 62 AML patients. CD105 (Endoglin) is a type I transmembrane protein which serves as an auxiliary receptor within the transforming growth factor (TGF) beta signalling complex and induces activation and proliferation of endothelial cells[7,8]. CD105 expression has been described in myelodysplastic syndrome (MDS), acute lymphoblastic leukaemia (ALL) and AML21–23, but its prognostic relevance in these and other haematopoietic malignancies has not been assessed so far. We here report on a newly generated CD105 antibody that was used to analyse CD105 expression in a cohort of 62 AML patients and identified a strong correlation of high CD105 expression with adverse disease outcome

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