[The relationship between abnormal MDR gene expression and chemotherapy response in lymphoid malignancies].
OBJECTIVE
To investigate the expression of multidrug resistance-1 (MDR(1)), Topoisomerase II (Topo II), glucocorticoid receptor (GCR) and their correlation with relapse rate and chemotherapy response in lymphoid malignancies.


METHODS
The expression of MDR(1), Topo II and GCR in 189 patients with lymphoid neoplasms was examined by RT-PCR, slot blot and ligand-labelled methods.


RESULTS
(1) The expressions of MDR(1), Topo II, GCR in untreated and relapsed/refractory patients with ALL, NHL, NHL-L, MM were significantly abnormal at varying levels, especially in the relapsed/refractory group. (2) The complete remission (CR) rate of MDR(1) high expression group (MDR(1)(+)) was significantly lower than that of MDR(1) negative expression (MDR(1)(-)) group (P < 0.05), and the relapse rate of MDR(1)(+) group was significantly higher than that of MDR(1)(-) group (P < 0.05). In untreated patients, the relapse rate in the Topo II low expression (Topo II(-)) group was positively higher than Topo II high expression (Topo II(+)) group (P < 0.05), whereas in the relapsed/refractory patients, the CR rate of Topo II(-) group was significantly lower than that of Topo II(+) group (P < 0.05). In the untreated and relapsed/refractory patients, the CR rates of low GCR expression (GCR(-)) group was obviously lower than that in the normal GCR expression group (P < 0.05). (3) Considering mono-drug resistance mechanism, CR rate of MDR(1)(+) group was the lowest, Topo II(-) group took the second place and GCR(-) group was the highest. As multiple drug resistance mechanisms coexisted, the CR rate of MDR(1)(+) + Topo II(-) + GCR(-) group and MDR(1)(+) + Topo II(-) group (11.1% and 15.4%, respectively) were significantly lower than that of MDR(1)(+), Topo II(-) and GCR(-) group (36.7%, 48.0% and 53.8%, respectively; P < 0.05 - P < 0.001).


CONCLUSIONS
There are primary and acquired drug resistance in lymphoid neoplasms. The high expression of MDR(1), low expression of Topo II and GCR are positively related to low chemotherapy response rate and high 2-year relapse rate. Co-analysis of MDR(1), Topo II and GCR may play an important role on chemotherapy response and prognostic judgment in lymphoid neoplasms.
Xu
Ying-chun
YC
Cancer Center of Renji Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
Lin
Yu-mei
YM
Zhang
Feng-chun
FC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012008:Recurrence; D012074:Remission Induction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D011965:Receptors, Glucocorticoid; D004250:DNA Topoisomerases, Type II