Expression of a Multidrug Resistance Gene in Blast Crisis of Chronic Myelogenous Leukemia

1989 ◽  
Vol 1 (2) ◽  
pp. 141-144 ◽  
Author(s):  
Robert Pirker ◽  
Lori J. Goldstein ◽  
Heinz Ludwig ◽  
Werner Linkesch ◽  
Christina Lechner ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Multidrug Resistance Gene

scholarly journals Inhibition of P-Glycoprotein and Recovery of Drug Sensitivity of Human Acute Leukemic Blast Cells by Multidrug Resistance Gene (mdr1) Antisense Oligonucleotides

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3163-3171
Author(s):  
Sayuri Motomura ◽  
Toshiko Motoji ◽  
Minoko Takanashi ◽  
Yan-Hua Wang ◽  
Hiroko Shiozaki ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Antisense Oligonucleotides ◽  
Inhibitory Effect ◽  
Resistant Cell Line ◽  
Myelogenous Leukemia ◽  
Multidrug Resistance Gene ◽  
P Glycoprotein ◽  
Blast Cells ◽  
Random Control

To overcome the problem of multidrug resistance, we investigated the effectiveness of phosphrothioate antisense oligonucleotides (MDR1-AS) in suppressing multidrug resistance gene (mdr1) expression in drug-resistant acute myelogenous leukemia (AML) blast cells and the K562 adriamycin-resistant cell line K562/ADM. The percentage of cells with the mdr1 gene product P-glycoprotein (P-gp) was decreased from 100% to 26% by 20 μmol/L MDR1-AS in the K562/ADM cells, and from 48.1% to 10.2% by 2.5 μmol/L MDR1-AS in the AML blast cells. Western blot analysis also showed a decrease in the amount of P-gp in the MDR1-AS–treated K562/ADM cells. This effect was specific to MDR1-AS, and not observed with sense or random control oligonucleotides. The expression of mdr1 mRNA in K562/ADM and AML blast cells treated with MDR1-AS was decreased compared with the random control. Intracellular rhodamine retention and [3H]daunorubicin also increased after antisense treatment. Chemosensitivity to daunorubicin increased in MDR1-AS–treated blast cells up to 5.9-fold in the K562/ADM cells and 3.0- to 6.4-fold in the AML blast cells. The expression of mdr1mRNA derived from colony cells decreased in the MDR1-AS–treated groups. No inhibitory effect of the oligonucleotides on normal bone marrow progenitors was observed. These findings suggest that MDR1-AS is useful to overcome multidrug resistance in the treatment of leukemia.

scholarly journals Inhibition of P-Glycoprotein and Recovery of Drug Sensitivity of Human Acute Leukemic Blast Cells by Multidrug Resistance Gene (mdr1) Antisense Oligonucleotides

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3163-3171 ◽  
Author(s):  
Sayuri Motomura ◽  
Toshiko Motoji ◽  
Minoko Takanashi ◽  
Yan-Hua Wang ◽  
Hiroko Shiozaki ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Antisense Oligonucleotides ◽  
Inhibitory Effect ◽  
Resistant Cell Line ◽  
Myelogenous Leukemia ◽  
Multidrug Resistance Gene ◽  
P Glycoprotein ◽  
Blast Cells ◽  
Random Control

Abstract To overcome the problem of multidrug resistance, we investigated the effectiveness of phosphrothioate antisense oligonucleotides (MDR1-AS) in suppressing multidrug resistance gene (mdr1) expression in drug-resistant acute myelogenous leukemia (AML) blast cells and the K562 adriamycin-resistant cell line K562/ADM. The percentage of cells with the mdr1 gene product P-glycoprotein (P-gp) was decreased from 100% to 26% by 20 μmol/L MDR1-AS in the K562/ADM cells, and from 48.1% to 10.2% by 2.5 μmol/L MDR1-AS in the AML blast cells. Western blot analysis also showed a decrease in the amount of P-gp in the MDR1-AS–treated K562/ADM cells. This effect was specific to MDR1-AS, and not observed with sense or random control oligonucleotides. The expression of mdr1 mRNA in K562/ADM and AML blast cells treated with MDR1-AS was decreased compared with the random control. Intracellular rhodamine retention and [3H]daunorubicin also increased after antisense treatment. Chemosensitivity to daunorubicin increased in MDR1-AS–treated blast cells up to 5.9-fold in the K562/ADM cells and 3.0- to 6.4-fold in the AML blast cells. The expression of mdr1mRNA derived from colony cells decreased in the MDR1-AS–treated groups. No inhibitory effect of the oligonucleotides on normal bone marrow progenitors was observed. These findings suggest that MDR1-AS is useful to overcome multidrug resistance in the treatment of leukemia.

Effect of MicroRNA145 on the multidrug resistance gene of ulcerative colitis in rats

Life Sciences ◽  
2021 ◽  
pp. 119603
Author(s):  
Ping Wangs ◽  
Yan Chen ◽  
La-Mei Zhang ◽  
Si-Qi Yuan ◽  
Shen-Ao Lu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Multidrug Resistance Gene

scholarly journals Modulation of the expression of a multidrug resistance gene (mdr-1/P-glycoprotein) by differentiating agents

1989 ◽  
Vol 264 (30) ◽  
pp. 18031-18040
Author(s):  
L A Mickley ◽  
S E Bates ◽  
N D Richert ◽  
S Currier ◽  
S Tanaka ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Multidrug Resistance Gene ◽  
P Glycoprotein ◽  
Differentiating Agents ◽  
Mdr 1

The biological significance of the multidrug resistance gene MRP in inversion 16 leukemias

1996 ◽  
Vol 20 (5-6) ◽  
pp. 357-364 ◽  
Author(s):  
Bryone J. Kuss ◽  
Roger G. Deeley ◽  
Susan P. C. Cole ◽  
Cheryl L. Willman ◽  
Kenneth J. Kopecky ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Biological Significance ◽  
Multidrug Resistance Gene

scholarly journals Structural Biology of Bacterial Multidrug Resistance Gene Regulators

2002 ◽  
Vol 277 (43) ◽  
pp. 40169-40172 ◽  
Author(s):  
Michael H. Godsey ◽  
Ekaterina E. Zheleznova Heldwein ◽  
Richard G. Brennan
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Structural Biology ◽  
Multidrug Resistance Gene

Congenital Juvenile Chronic Myelogenous Leukemia: Case Report and Review

PEDIATRICS ◽  
1984 ◽  
Vol 73 (3) ◽  
pp. 324-326
Author(s):  
Reese H. Clark ◽  
Leslie L. Taylor ◽  
Robert J. Wells
Keyword(s):  
Bone Marrow ◽  
Case Report ◽  
Chronic Myelogenous Leukemia ◽  
Peripheral Blood ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Juvenile Form

The case of a patient with ecchymosis, hepatomegaly, leukocytosis, thrombocytopenia, and anemia at birth is presented. Throughout his course, thrombocytopenia, anemia, and leukocytosis without a marked increase in the number of blast forms in either peripheral blood or bone marrow persisted until the patient developed a blast crisis shortly before his death at age 4 months. This patient is the youngest reported to have the juvenile form of chronic myelogenous leukemia and the first that in the present era can be considered congenital in origin.

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