Endoglin: a novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models.
Keina M C DouradoJune BaikVanessa K P OliveiraMiriam BeltrameAmi YamamotoCharles P TheuerCamila A V FigueiredoMichael R VernerisRita C R PerlingeiroPublished in: Blood (2017)
Endoglin (CD105), a receptor of the transforming growth factor-β superfamily, has been reported to identify functional long-term repopulating hematopoietic stem cells, and has been detected in certain subtypes of acute leukemias. Whether this receptor plays a functional role in leukemogenesis remains unknown. We identified endoglin expression on the majority of blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL). Using a xenograft model, we find that CD105+ blasts are endowed with superior leukemogenic activity compared with the CD105- population. We test the effect of targeting this receptor using the monoclonal antibody TRC105, and find that in AML, TRC105 prevented the engraftment of primary AML blasts and inhibited leukemia progression following disease establishment, but in B-ALL, TRC105 alone was ineffective due to the shedding of soluble CD105. However, in both B-ALL and AML, TRC105 synergized with reduced intensity myeloablation to inhibit leukemogenesis, indicating that TRC105 may represent a novel therapeutic option for B-ALL and AML.
Keyphrases
- acute myeloid leukemia
- liver failure
- allogeneic hematopoietic stem cell transplantation
- transforming growth factor
- stem cells
- respiratory failure
- monoclonal antibody
- drug induced
- epithelial mesenchymal transition
- nk cells
- randomized controlled trial
- aortic dissection
- binding protein
- bone marrow
- mouse model
- cancer therapy
- high intensity
- cell therapy
- transcription factor