The Prognostic Significance Of Expression Of BFGF/GF-R1 And Its Relationship With Apoptosis And Drug-resistance In Patients With Acute Leukemia

Objective: To measure the level of serum basic Fibroblast Growth Factor (bFGF) in acute leukemia and examine the expression of bFGF/FGF-Rl in leukemic cells, to study its prognostic significance and its relationship with the proliferation >. apoptosis and drug resistance of leukemic cells. To study leukemia from hematopoietic micrenviroment so as to have a new strategy for the treatment of leukemia.Methords: We quantitate the serum bFGF in patients with acute leukemia by ELISA ; examine the gene expression of bFGF , FGF-R1 and MRP in bone marrow samples of patients and in leukemic cell lines (K562^ HL-6CK U937) by RT-PCR ; measure the expression levels of bcl-2, Bax, CD33, CD34 in bone marrow samples with leukemia by flow cytometry, and calculate the proliferation index (PI) from the results of DNA analysis.Results: 1. The mean level of serum bFGF in AL is 60.05pg/ml, much higher than that of the normal contrals (9pg/ml) with significant difference , P<0.01; The mean level of serum bFGF in CR-patients is 81.2pg/ml , much higher than that of the normal controls (9pg/ml) withsignificant difference , while compared with the AL , there isn't any significant difference (p>0.05); The elevation ratios of bFGF in AL (65.91%) and in CR-patients (100%) are higher than those in normal controls (8.3%), P<0.05; The remission ratio of patients with high serum bFGF level (44%) is much lower than that of the patients with normal serum bFGF levels (73.33%), with significant difference, P< 0.05; the relapse ratio of patients with high level of serum bFGF (90.51%) is higher than that of patients with normal serum bFGF (40.51%), with significant difference, P<0.05.2. 82% of the AL have bFGF expression , the mean level is 0.452, much higher than that of the normal controls (0.142) with significant difference, P<0.05, there is a positive correlation between the expression levels of bFGF mRNA and the serum bFGF levels r=0.465, P<0.05; The K562 cell line and 57% of the patients express both bFGF and FGF-R1 , indicating that bFGF/FGF-Rl may play a role in the autocrine/paracrine mechanisms of leukemic cells.3.There is a positive correlation between serum bFGF and the proliferation index (PI) of the bone marrow cells in AL r=0.5915,p<0.01 .4. A positive correlation could also be found between the levels of serum bFGF and the expression levels of bcl-2 in bone marrow cells in AL, r=0.4708 P<0.05 .5.In AL patients, the mean serum bFGF level in MRP+ patients (65.33pg/ml) is higher than that in MRP- patients,indicating the possibility that MRP may play a role in the secration of bFGF.Conclusion: The serum bFGF levels are elevated in AL , the leukemic cell is one of the source of the bFGF, MRP may play a role in the secration. The bFGF in the microenviroment could promote the proliferation of the leukemic cells, inhibit their apoptosis and have the cells to resist to anticancer drugs, so as the patients have a bad prognosis. With the bFGF as example, the abnomability of hamotopoietic microenviroment may play a role in leukemia.