| Objective: To investigate the clinical significance of the expression of p-glycoprotein (p-gp) and Bcl-2 protein in acute leukemia (AL) and chronic myelogenous leukemia(CML).Methods: The expression rates of p-gp and Bcl-2 in bone marrow mononuclear cells(BMMNC) from 97 patients with AL and 26 patients with CML were detected by flow cytometry with direct immunofluorescent labeling.Results: (1)The percentages of P-gp and Bcl-2 protein positive cells in AL were significantly higher than those of normal control group(52.57% versus 20%,P<0.01；42.27% versus 15%,P<0.025). (2)The expression of p-gp was higher in patients with refractory/relapsed AML than that of patients with AML untreated(84.6% versus 50%, P<0.025). The positive percentage of Bcl-2 on refractory/relapsed ALL was higher than that at previously untreated patients(75% versus 31.8%,P<0.05). (3)The higher expression of p-gp and Bcl-2 were observed in M4 and M5 subtype of AML. However, the expression percentage of p-gp and Bcl-2 was lower in M3 subtype(P<0.05). (4)The complete remission (CR) rate in patients with p-gp+ is lower than that in patients with p-gp-(60.6% versus 85.71%,P<0.05). There was no significant difference in the CR rate between patients with Bcl-2+ and Bcl-2- patients(68% versus 76.74%,P>0.05).Patients with P-gp+/Bcl-2+ were of higher CR rate than ones with P-gp-/Bcl-2-(46.15% versus 87.5%,P<0.05). (5)The early relapse rates of patients with p-gp+ and Bcl-2+ were higher than that of patients with p-gp- and Bcl-2-(70% versus 13.13%,P<0.005；64.71% versus 21.21%,P<0.05). Compared with patients with p-gp-/Bcl-2-,the patients with p-gp+/Bcl-2+ were characteristic of lower CR rate and higher early relapse rate(87.5% versus 9.52%,P<0.005). (6)There were no correlation between p-gp and Bcl-2(r=0.04391,P>0.05;r=0.10828,P>0.05). (7)The positive rate of expression of Bcl-2 protein was much higher in aggressive or blastic phase than in chronic phase (77.78% versus 41.17%,P＜0.05)；But there was no statistical difference in the expression of p-glycoprotein between aggressive or blastic phase and chronic phase(4.44% versus 29.42%,P＞0.05). (8) 4 of 7 BC-CML patients finishied standard induction chemotherapy. 3 patients with p-gp＋did not respond to therapy(NR) with mitoxantrone and arabinosyl cytosine .However, one patient with p-gp- achieved complete remission(CR). Conclusions:(1). The expressions of P-gp and Bcl-2 protein in AL patients were higher than that of normal control group. (2)The clinical drug-resistance of AML is closely associated with P-gp , while that of ALL is mainly associated with Bcl-2 .(3) The overexpression of Bcl-2 or p-gp could result in poor prognosis of AL. The measurement of p-gp combined with Bcl-2 may be more valuable to evaluate the prognosis of AL.(4) The overexpression of Bcl-2 protein provides an experimental basis for early diagnosis of CML blastic crisis. Bcl-2 probably play an important role in the acute transformation of chronic myelogenous leukemia. (5) By different mechanisms, both P-gp and Bcl-2 can mediate clinical drug-resistance of AL. (6) P-gp may be regarded as an unfavorable prognostic factor in BC-CML patients, howerer, p-gp was not associtated with acute transormation of CML. |
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