scholarly journals Multi-drug resistance (MDR1) gene expression in de novo acute leukemia cells: correlations with CD surface markers and treatment outcome

1998 ◽  
Vol 13 (6) ◽  
pp. 617 ◽  
Author(s):  
E Z Jiang ◽  
Y J Chang ◽  
J W Lee ◽  
W K Lee ◽  
J S Kim ◽  
...  
Blood ◽  
1993 ◽  
Vol 82 (11) ◽  
pp. 3445-3451 ◽  
Author(s):  
H Miwa ◽  
K Kita ◽  
K Nishii ◽  
N Morita ◽  
N Takakura ◽  
...  

Abstract MDR1 gene expression was examined in acute leukemia cells from 75 Japanese patients at diagnosis (50 with acute myeloblastic leukemia [AML]: 10 M1, 18 M2, 5 M3, 8 M4, 9 M5; 25 with acute lymphoblastic leukemia [ALL]: 13 B-precursor, 12 T-lineage). The results of MDR1 mRNA expression by reverse transcriptase polymerase chain reaction were confirmed by immunostaining using the anti-P-glycoprotein monoclonal antibody UIC2 and by a functional study using the rhodamine efflux test. Morphologically, AML M1 cases had the highest incidence of MDR1 gene expression (6 of 10 patients). Phenotypically, CD7 and CD34 were the only surface markers that were significantly associated with MDR1 gene expression (P < .01). In CD7+CD4-CD8- ALL, which is thought to originate from the lymphohematopoietic stem cell, expressed the MDR1 gene with a high incidence (six of eight patients), whereas three surface CD3+ and one CD4+CD8+ T-cell ALL (T-ALL) did not have detectable MDR1 transcripts. Only two cases of 13 B-precursor ALL had MDR1 mRNA, one of which had the Philadelphia (Ph1) chromosome. No association was observed between MDR1 gene expression and CD34 positivity in ALL. Our results that MDR1 mRNA was frequently expressed in CD7+ AML and CD7+CD4-CD8- ALL, together with the previous reports indicating clinical similarities between these leukemias, provides a clue to clarify a relationship between CD7+ AML and CD7+CD4-CD8- ALL. In addition, MDR1 expression in CD7+ AML/ALL might be responsible for the poor response to conventional chemotherapies of these types of leukemia.


Blood ◽  
1993 ◽  
Vol 82 (11) ◽  
pp. 3445-3451
Author(s):  
H Miwa ◽  
K Kita ◽  
K Nishii ◽  
N Morita ◽  
N Takakura ◽  
...  

MDR1 gene expression was examined in acute leukemia cells from 75 Japanese patients at diagnosis (50 with acute myeloblastic leukemia [AML]: 10 M1, 18 M2, 5 M3, 8 M4, 9 M5; 25 with acute lymphoblastic leukemia [ALL]: 13 B-precursor, 12 T-lineage). The results of MDR1 mRNA expression by reverse transcriptase polymerase chain reaction were confirmed by immunostaining using the anti-P-glycoprotein monoclonal antibody UIC2 and by a functional study using the rhodamine efflux test. Morphologically, AML M1 cases had the highest incidence of MDR1 gene expression (6 of 10 patients). Phenotypically, CD7 and CD34 were the only surface markers that were significantly associated with MDR1 gene expression (P < .01). In CD7+CD4-CD8- ALL, which is thought to originate from the lymphohematopoietic stem cell, expressed the MDR1 gene with a high incidence (six of eight patients), whereas three surface CD3+ and one CD4+CD8+ T-cell ALL (T-ALL) did not have detectable MDR1 transcripts. Only two cases of 13 B-precursor ALL had MDR1 mRNA, one of which had the Philadelphia (Ph1) chromosome. No association was observed between MDR1 gene expression and CD34 positivity in ALL. Our results that MDR1 mRNA was frequently expressed in CD7+ AML and CD7+CD4-CD8- ALL, together with the previous reports indicating clinical similarities between these leukemias, provides a clue to clarify a relationship between CD7+ AML and CD7+CD4-CD8- ALL. In addition, MDR1 expression in CD7+ AML/ALL might be responsible for the poor response to conventional chemotherapies of these types of leukemia.


1991 ◽  
Vol 83 (10) ◽  
pp. 708-712 ◽  
Author(s):  
R. Pirker ◽  
J. Wallner ◽  
K. Geissler ◽  
W. Linkesch ◽  
O. A. Haas ◽  
...  

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4677-4677
Author(s):  
Bing Xu ◽  
Xiaoyan Song ◽  
Pengcheng Shi ◽  
Pengnan Xiao ◽  
Zhengshan Yu ◽  
...  

Abstract Abstract 4677 Introdution The expression of CD56 antigen and over-expression of the multidrug resistance gene 1 (MDR1) seems to confer the poor therapeutic outcome to AML. The aim of this study is to investigate the relationship between CD56 antigen expression and MDR1 gene expression in patients with de novo AML and explore the indicating effect of these two factors on clinical drug resistance. Patients and methods A real-time quantitative reverse transcriptase polymerase chain reaction method was established for detecting MDR1 expression levels and a three-color flow cytometry analysis with CD45/SSC gating was used to examine CD56 antigen expression in 79 patients with de novo AML. Results CD56 antigen was recorded in 19 out of 79 cases (24.1%) and particularly in those with M5 subtype and t(8;21) AML. Moreover, CD56 expression was significantly associated with unfavorable cytogenetic abnormalities (P< 0.05). Significantly higher percentage (57.1%, 4/7) of patients with t(8;21) demonstrated CD56 expression than those with favorable cytogenetic abnormalities (P< 0.05). CD56+ AML patients had higher incidence of splenohepatomegalia and level of lactate dehydrogenase than CD56- patients (P< 0.05). The median expression level of MDR1 was statistically higher in CD56+ AML patients than that in CD56- cases (P< 0.001) and 89.5% (17/19) CD56+ AML patients were found with high MDR1 expression. The CR rate in high MDR1 / CD56+ AML patients was significantly lower than that in low MDR1/ CD56- cases. (58.8% vs 89.2%, P< 0.01). Conclusions There is a linear correlation between MDR1 and CD56 expression in AML. This relationship may explain why CD56 expression is related to a poor prognosis in AML. Therefore both with high MDR1 expression level and CD56 antigen expression can identify AML patients with unfavorable outcome. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 586-592 ◽  
Author(s):  
JP Marie ◽  
R Zittoun ◽  
BI Sikic

Resistance to multiple chemotherapeutic agents has been related to the production of P-glycoprotein, a trans-membrane drug efflux pump that is encoded by the multidrug resistance (MDR) gene mdr1. To investigate whether mdr1 could be involved in clinical resistance to chemotherapy in acute leukemias, we have analyzed retrospectively the RNA from adult acute leukemia cells by slot-blot hybridization with a human mdr1 probe. Units of mdr1 expression were defined by reference to drug- sensitive human sarcoma and K562 leukemia cell lines (1 U) and the highly resistant doxorubicin selected leukemia cells K562/R7 (50 U). We studied 41 adult patients with acute leukemias: 5 acute lymphoblastic leukemias, 23 acute myeloid leukemias, and 13 secondary leukemias or blast crisis of chronic myelogenous leukemia. Expression of 10 U or more of mdr1 was found in 6 of 31 (19%) leukemias at diagnosis, versus 5 of 10 (50%) after relapse from therapy, P = .06. The complete remission rate and in vitro sensitivity to daunorubicin were both correlated with low expression (1 U, v 2 U or more) of mdr1. Among 36 evaluable attempts to induce remission, the complete remission rate was 67% (8 of 12) for patients with undetectable or minimal mdr1 expression (1 U), versus 29% (7 of 24) in patients with 2 U or more of expression, P = .03. In vitro resistance to daunorubicin or other MDR-related drugs was associated with expression of 2 U or more of mdr1 in 11 of 11 cases, while specimens that were sensitive to these agents were negative for mdr1 expression in 5 of 11 cases, P = .03. These data suggest that mdr1 expression contributes to chemoresistance in acute leukemia. Determination of mdr1 gene expression may be useful in designing therapy for patients with leukemia.


Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 586-592 ◽  
Author(s):  
JP Marie ◽  
R Zittoun ◽  
BI Sikic

Abstract Resistance to multiple chemotherapeutic agents has been related to the production of P-glycoprotein, a trans-membrane drug efflux pump that is encoded by the multidrug resistance (MDR) gene mdr1. To investigate whether mdr1 could be involved in clinical resistance to chemotherapy in acute leukemias, we have analyzed retrospectively the RNA from adult acute leukemia cells by slot-blot hybridization with a human mdr1 probe. Units of mdr1 expression were defined by reference to drug- sensitive human sarcoma and K562 leukemia cell lines (1 U) and the highly resistant doxorubicin selected leukemia cells K562/R7 (50 U). We studied 41 adult patients with acute leukemias: 5 acute lymphoblastic leukemias, 23 acute myeloid leukemias, and 13 secondary leukemias or blast crisis of chronic myelogenous leukemia. Expression of 10 U or more of mdr1 was found in 6 of 31 (19%) leukemias at diagnosis, versus 5 of 10 (50%) after relapse from therapy, P = .06. The complete remission rate and in vitro sensitivity to daunorubicin were both correlated with low expression (1 U, v 2 U or more) of mdr1. Among 36 evaluable attempts to induce remission, the complete remission rate was 67% (8 of 12) for patients with undetectable or minimal mdr1 expression (1 U), versus 29% (7 of 24) in patients with 2 U or more of expression, P = .03. In vitro resistance to daunorubicin or other MDR-related drugs was associated with expression of 2 U or more of mdr1 in 11 of 11 cases, while specimens that were sensitive to these agents were negative for mdr1 expression in 5 of 11 cases, P = .03. These data suggest that mdr1 expression contributes to chemoresistance in acute leukemia. Determination of mdr1 gene expression may be useful in designing therapy for patients with leukemia.


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