Journal Article

Prognostic and biological significance of the proangiogenic factor EGFL7 in acute myeloid leukemia

Karunasiri, Malith, Burke, Matthew H., Ozer, Hatice Gulcin, Wang, Eunice S., Powell, Bayard L., Bill, Marius, Yilmaz, Selen A., Marcucci, Guido, Carter, Thomas H., Dorrance, Adrienne M., Nicolet, Deedra, Behbehani, Gregory K., Garzon, Ramiro, Oakes, Christopher C., Croce, Carlo M., McNeil, Betina, Kolitz, Jonathan E., Steiner, Damian J., Shen, Changxian, Caligiuri, Michael A., Zitzer, Nina, Mrózek, Krzysztof, Papaioannou, Dimitrios, Bloomfield, Clara D.

2017

Overview

Epithelial growth factor-like 7 (EGFL7) is a protein that is secreted by endothelial cells and plays an important role in angiogenesis. Although EGFL7 is aberrantly overexpressed in solid tumors, its role in leukemia has not been evaluated. Here, we report that levels of both EGFL7 mRNA and EGFL7 protein are increased in blasts of patients with acute myeloid leukemia (AML) compared with normal bone marrow cells. High EGFL7 mRNA expression associates with lower complete remission rates, and shorter event-free and overall survival in older (age ≥60 y) and younger (age <60 y) patients with cytogenetically normal AML. We further show that AML blasts secrete EGFL7 protein and that higher levels of EGFL7 protein are found in the sera from AML patients than in sera from healthy controls. Treatment of patient AML blasts with recombinant EGFL7 in vitro leads to increases in leukemic blast cell growth and levels of phosphorylated AKT. EGFL7 blockade with an anti-EGFL7 antibody reduced the growth potential and viability of AML cells. Our findings demonstrate that increased EGFL7 expression and secretion is an autocrine mechanism supporting growth of leukemic blasts in patients with AML.

• Publisher: National Academy of Sciences
• Subject: Aberration / Acute myeloid leukemia / Adult / Age Factors / Aged / Aged, 80 and over / AKT protein / Angiogenesis / Angiogenic Proteins - antagonists & inhibitors / Angiogenic Proteins - genetics / Angiogenic Proteins - metabolism / Animals / Antibodies, Blocking - pharmacology / Autocrine signalling / Biological Sciences / Bone marrow / Calcium-Binding Proteins / Case-Control Studies / Cell Line, Tumor / Cell Proliferation / Cells / Disease-Free Survival / EGF Family of Proteins / Endothelial cells / Endothelial Growth Factors - antagonists & inhibitors / Endothelial Growth Factors - genetics / Endothelial Growth Factors - metabolism / Female / Fibroblast growth factor 2 / Gene expression / Humans / Leukemia / Leukemia, Myeloid, Acute - genetics / Leukemia, Myeloid, Acute - metabolism / Leukemia, Myeloid, Acute - therapy / Male / Medical Sciences / Mice / MicroRNAs - genetics / MicroRNAs - metabolism / Middle Aged / Myeloid leukemia / Patients / PNAS Plus / Prognosis / Proteins / Proteins - metabolism / Proteins - pharmacology / Recombinant Proteins - metabolism / Recombinant Proteins - pharmacology / Remission / Ribonucleic acid / Risk Factors / RNA / RNA, Messenger - genetics / RNA, Messenger - metabolism / Secretion / Solid tumors / Tumors / Up-Regulation / Viability / Young Adult