Clinical Implication of Bone Marrow Angiogenesis in Childhood Acute Lymphocytic Leukemia.

Purpose: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are associated with increased angiogenesis, growth, and metastasis in solid tumors. But, until today, the importance of theses factors on leukemia, especially childhood acute lymphocytic leukemia (ALL) has received limited attention. Therefore, this study examined the bone marrow plasma VEGF and bFGF levels in ALL patients and normal controls.

Methods: Bone marrow plasmas at diagnosis from 33 ALL patients (median age 5.97 years; range 1.8–13.9 years) were used for analysis. All ALL patients are divided into 3 groups; one group is standard risk ALL, other group is high risk ALL who did not experience relapse, and the other group is high risk ALL who have experienced relapse during treatment. The bone marrow levels of bFGF and VEGF were determined by enzyme-linked immunosorbent assay (R & D Systems) and compared with the bone marrow levels of 7 healthy control subjects (median age 11.98 years; 6 months–13.6 years).

Results: The VEGF levels were higher in high risk ALL with relapse (N=7, 171.95 ± 202.54 pg/mL) compared with standard risk (N=9, 9.11 ± 21.47 pg/mL), high risk ALL without relapse (N=17, 37.09 ± 38.77 pg/mL) or normal control (N=7, 72.9 ± 68.22 pg/mL)(P=0.006).

View largeDownload slide

Figure

View largeDownload slide

Figure

Close modal

The bFGF levels were also significantly higher in high risk ALL patients who experienced relapse (high risk with relapse; 37.26 ± 35.73 pg/mL, standard risk ALL; 7.90 ± 12.99 pg/mL, high risk ALL without relapse; 7.27 ± 10.93 pg/mL, normal control; 6.39 ± 6.13 pg/mL) (P=0.003).

View largeDownload slide

Figure

View largeDownload slide

Figure

Close modal

The Pearson correlation coefficient between VEGF and bFGF was 0.775 (P < 0.01). Three patients who showed high levels of both angiogenic markers (VEGF; 366.80 ± 141.29 pg/mL, bFGF; 70.27 ± 5.57 pg/mL) are relapsed and died due to disease progression. The other relapsed patients except these 3 patients are alive without disease after salvage chemotherapy.

Conclusion: Our data suggest that the increased levels of VEGF and bFGF in bone marrow may play an important role in estimating prognosis of childhood ALL.