Evaluation and Clinical Correlation of Bone Marrow Angiogenesis and Levels of Serum Angiogenic Factors in Acute Leukemia
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- Category: Vol. 77, September 2009
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Evaluation and Clinical Correlation of Bone Marrow Angiogenesis and Levels of Serum Angiogenic Factors in Acute Leukemia,AMIRA M. KHORSHID, KHALED M. ABOUL ENEIN, SONYA F. ARSANYOS, IMAN A. ABDEL GAWAD, OLA M. EL DESSOUKY, HALA M.R. HASSANEIN and GEHAN M. MAHMOUD
Abstract
In this study serum angiogenic factors [vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and tumour necrosis factor a (TNF a)] and cellular angiogenic factors (VEGF and VEGF-R2) were studied in 50 newly diagnosed acute leukemia patients, they were 24 ALL and 26 AML patients. The correlations of the studied angiogenic factors to each other and to the patients’ survival and disease outcome were studied. During the follow-up period of 6 months, 22 patients died and 28 patients remained alive from whom 11 patients were refractory and 17 patients achieved complete remission.
On comparison between pretreatment concentration levels of measured serum angiogenic factors (VEGF, TNF-a and HGF) in ALL, AML and the control group, all the comparisons were statistically significant (p<0.0001, <0.0001 and 0.021 respectively). All serum markers were higher in AML group than control group, but only VEGF showed statistically significant elevation (p<0.0001), while in ALL patients, all markers were significantly higher than control group (p=0.01).
When comparing ALL and AML cases according to cellular angiogenic factors detected by immunocytochemistry, cellular VEGF-R2 was slightly higher in ALL group, while cellular VEGF was slightly higher in AML group. The comparisons were statistically non-significant for both angiogenic factors.
As regards response to therapy, in ALL, cases with high sVEGF showed a statistically significant lower rate of complete remission than cases with low sVEGF (p=0.041). The same results were obtained for AML but the comparison did not reach a significant level (p=0.082).
Serum VEGF was the only reliable marker to predict relapse in ALL (p=0.009) and AML (p=0.049).
On comparing serum VEGF to the outcome in ALL, high sVEGF cases showed a statistically significant higher rate of death than low sVEGF cases (p=0.05), while in AML, the same results were obtained but the comparison did not reach a significant level.
As regards the survival time, cases with low sVEGF level showed higher mean survival and 6-month survival than cases with high sVEGF level (p=0.03).
A significant negative correlation was detected between serum VEGF and serum TNF-a (correlation coefficient (r) =–0.642, p<0.0001).
Conclusion: Serum angiogenic factors (VEGF, TNF-a and HGF) are markedly increased in cases of acute leukemia compared to normal controls. Cases with high sVEGF showed higher rate of death than cases with low sVEGF, so its targeting may provide a potent novel therapeutic approach in acute leukemias. VEGF may also be useful as a new prognostic factor and a predictor of relapse in different types of acute leukemia. Further studies with larger number of patients and longer duration of follow-up are recommended to throw more light on the significance of other angiogenic factors in relation to acute leukemia.