Endoglin: A novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models

Keina M.C. Dourado, June Baik, Vanessa K.P. Oliveira, Miriam Beltrame, Ami Yamamoto, Charles P. Theuer, Camila A.V. Figueiredo, Michael R. Verneris, Rita C.R. Perlingeiro

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Endoglin (CD105), a receptor of the transforming growth factor-b 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. Wetest the effect of targeting this receptor using themonoclonal antibody TRC105, and find that in AML, TRC105 prevented the engraftment of primary AML blasts and inhibited leukemiaprogression 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 mayrepresent anovel therapeutic option for B-ALL and AML.

Original languageEnglish (US)
Pages (from-to)2526-2536
Number of pages11
JournalBlood
Volume129
Issue number18
DOIs
StatePublished - May 4 2017

Bibliographical note

Funding Information:
The authors are grateful to the Heme Malignancy Tissue Bank at the University of Minnesota. The authors thank Cynthia Dekay for assistance in graphic design. This work was supported by a seed grant from the University of Minnesota Academic Health Sciences (R.C.R.P.), by funds from TRACON Pharmaceutical (R.C.R.P.), and by National Institutes of Health National Heart, Lung, and Blood Institute grant 2T32HL007062 (J.B.). The Heme Malignancy Tissue Bank at the University of Minnesota receives support from the National Cancer Institute (NCI no. 5P30CA077598-18), and from the Minnesota Masonic Charities and the Killebrew-Thompson Memorial Fund through the Cancer Experimental Therapeutics Initiative.

Publisher Copyright:
© 2017 by The American Society of Hematology.

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