Blood, 15 December 2002, Vol. 100, No. 13, pp. 4256-4256
Leukemia cells eat their VEGFtables
The importance of angiogenesis in supporting and
promoting tumor growth in solid tumors has been established for many
years. But angiogenesis was until recently not thought to play a role in leukemias. Several studies have now shown increased vascularity in
the bone marrow and increased VEGF plasma levels in patients with leukemia and VEGF receptors in leukemia cells. Clinically, elevated cellular levels of VEGF are associated with a poor prognosis in AML.
We are now starting to understand the biologic effects of
angiogenesis in leukemia. It has been shown that VEGF can stimulate leukemia cell growth in vitro. Schuch et al (page 4622) now show the
role of VEGF in promoting leukemia growth in vivo with 2 animal models.
The first is a SCID mouse model injected subcutaneously with M1 cells
that develop chloromas. Using a novel delivery system for release of
VEGF or its antagonist, they demonstrate significant growth of the
tumors with a rich capillary network promoted by VEGF. They use
as a VEGF antagonist a soluble version of the extracellular portion of neuropilin-1 (NRP-1) that can bind circulating VEGF. sNRP-1
inhibited the growth of chloromas. The second model is a systemic
leukemia model in SCID mice injected intravenously with M1 cells.
Again, VEGF promoted and sNRP-1 inhibited leukemia progression.
These findings are significant in many ways. First, they demonstrate
quite convincingly in vivo the opposing effects of VEGF and anti-VEGF
in leukemia progression. An interesting observation in this study is
that these results come from a model that uses a cell line (M1) that
does not directly respond to VEGF. This suggests that the effect is not
through direct stimulation of leukemia cell growth by VEGF, but rather
that angiogenesis itself plays a role in leukemia growth. The exact
mechanism by which angiogenesis supports leukemia progression remains
to be determined. Second, it shows the potential of sNRP-1 as an
antiangiogenic strategy that should be investigated further. Other
antiangiogenic agents are already in clinical trials, including
anti-VEGF monoclonal antibodies and VEGF-receptor inhibitors. These
molecules may have a role in the management of AML. One major challenge
will be the proper design and evaluation of clinical trials that would
incorporate these agents. Finally, the microencapsulation technology
used in this study may offer a new way to investigate similar peptides in the future.
Jorge Cortes
M. D. Anderson Cancer Center
