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Blood, Vol. 95 No. 8 (April 15), 2000:
pp. 2637-2644
Increased angiogenesis in the bone marrow of patients with
acute myeloid leukemia
Teresa Padró,
Sandra Ruiz,
Ralf Bieker,
Horst Bürger,
Martin Steins,
Joachim Kienast,
Thomas Büchner,
Wolfgang E. Berdel, and
Rolf M. Mesters
From the Department of Medicine/Hematology and Oncology and the
Gerhard-Domagk Institute of Pathology, University of Muenster,
Muenster, Germany.
The importance of angiogenesis for the progressive growth and
viability of solid tumors is well established. In contrast, only few
data are available for hematologic neoplasms. To investigate the role
of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies
from 62 adults with newly diagnosed, untreated AML (day 0) were
evaluated. Further studies were done after the completion of remission
induction chemotherapy (day 16 of induction chemotherapy, n = 21;
complete remission, n = 20). Microvessels were scored in at least 3 areas (×500 field, 0.126 mm2) of the highest
microvessel density in representative sections of each bone marrow
specimen using immunohistochemistry for von Willebrand factor and
thrombomodulin. Microvessel counts were significantly higher in
patients with AML (n = 62) compared with control patients
(n = 22): median (interquartile range) 24.0 (21.0-27.8)/×500 field vs 11.2 (10.0-12.0)/×500 field, respectively
(P < .001). On day 16 of induction chemotherapy,
microvessel density was reduced by 60% (44-66) (P < .001)
in hypoplastic marrows without residual blasts, in contrast to only
17% (0-37) reduction in hypoplastic marrows with  5% residual
blasts (P < .001 for the difference between both groups).
Bone marrow biopsies taken at the time of complete remission displayed
a microvessel density in the same range as the controls. In conclusion,
there is evidence of increased microvessel density in the bone marrow
of patients with AML, which supports the hypothesis of an important
role of angiogenesis in AML. Furthermore, these findings suggest that
antiangiogenic therapy might constitute a novel strategy for the
treatment of AML.
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