Fig. 1.

Autocrine VEGF signaling in AML cells. VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 are overexpressed by AML blasts. VEGF-A and VEGF-C proteins can pass the cell membrane through active transport using secretory vesicles. Studies in endothelial cells demonstrated that VEGFR-2 in the cytoplasm is captured within the endosomes, which is also likely for VEGFR-3 [82]. The cytoplasmic VEGFR-2 retains its signaling activity, even when trapped within the endosomes. Excretion of VEGF-A/C enables the AML cell to bind VEGF-A/C to the VEGFR-2, residing on the cell membrane (external loop). Moreover, VEGF-A/C can also signal internally through binding to VEGFR-2 and VEGFR-3 that reside in the cytoplasm (internal loop). The role of VEGFR-2 within the nucleus is unknown