|
|
 Previous Article | Table of Contents | Next Article 
Multidrug resistance (mdr1) gene expression in adult acute leukemias:
correlations with treatment outcome and in vitro drug sensitivity
JP Marie, R Zittoun and BI Sikic
Department of Medicine, Stanford University School of Medicine, CA.
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.
Volume 78,
Issue 3,
pp. 586-592,
08/01/1991
Copyright © 1991 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Yokota, S. Kimura, S. Masuda, E. Ashihara, J. Kuroda, K. Sato, Y. Kamitsuji, E. Kawata, Y. Deguchi, Y. Urasaki, et al.
INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity
Blood,
January 1, 2007;
109(1):
306 - 314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Ludwig, G. Szakacs, S. E. Martin, B. F. Chu, C. Cardarelli, Z. E. Sauna, N. J. Caplen, H. M. Fales, S. V. Ambudkar, J. N. Weinstein, et al.
Selective Toxicity of NSC73306 in MDR1-Positive Cells as a New Strategy to Circumvent Multidrug Resistance in Cancer.
Cancer Res.,
May 1, 2006;
66(9):
4808 - 4815.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mahadevan and A. F. List
Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies
Blood,
October 1, 2004;
104(7):
1940 - 1951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Greenberg, S. J. Lee, R. Advani, M. S. Tallman, B. I. Sikic, L. Letendre, K. Dugan, B. Lum, D. L. Chin, G. Dewald, et al.
Mitoxantrone, Etoposide, and Cytarabine With or Without Valspodar in Patients With Relapsed or Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome: A Phase III Trial (E2995)
J. Clin. Oncol.,
March 15, 2004;
22(6):
1078 - 1086.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Solary, B. Drenou, L. Campos, P. de Cremoux, F. Mugneret, P. Moreau, B. Lioure, A. Falkenrodt, B. Witz, M. Bernard, et al.
Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia
Blood,
August 15, 2003;
102(4):
1202 - 1210.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tafuri, C. Gregorj, M. T. Petrucci, M. R. Ricciardi, M. Mancini, G. Cimino, C. Mecucci, A. Tedeschi, G. Fioritoni, F. Ferrara, et al.
MDR1 protein expression is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia
Blood,
July 18, 2002;
100(3):
974 - 981.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Perel, A. Auvrignon, T. Leblanc, J.-P. Vannier, G. Michel, B. Nelken, V. Gandemer, C. Schmitt, J.-P. Lamagnere, L. De Lumley, et al.
Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91
J. Clin. Oncol.,
June 15, 2002;
20(12):
2774 - 2782.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Palmedo
What Can We Expect from MDR Breast Cancer Imaging with Sestamibi?
J. Nucl. Med.,
April 1, 2002;
43(4):
526 - 530.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Kang, W. D. Figg, Y. Ando, M. V. Blagosklonny, D. Liewehr, T. Fojo, and S. E. Bates
The P-Glycoprotein Antagonist PSC 833 Increases the Plasma Concentrations of 6{{alpha}}-Hydroxypaclitaxel, a Major Metabolite of Paclitaxel
Clin. Cancer Res.,
June 1, 2001;
7(6):
1610 - 1617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. van den Heuvel-Eibrink, E. A. C. Wiemer, M. J. de Boevere, B. van der Holt, P. J. M. Vossebeld, R. Pieters, and P. Sonneveld
MDR1 gene-related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia
Blood,
June 1, 2001;
97(11):
3605 - 3611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Filipits, U. Jaeger, I. Simonitsch, C. Chizzali-Bonfadin, H. Heinzl, and R. Pirker
Clinical Relevance of the Lung Resistance Protein in Diffuse Large B-Cell Lymphomas
Clin. Cancer Res.,
September 1, 2000;
6(9):
3417 - 3423.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. M. van der Kolk, E. G. E. de Vries, W. L. J. van Putten, L. F. Verdonck, G. J. Ossenkoppele, G. E. G. Verhoef, and E. Vellenga
P-glycoprotein and Multidrug Resistance Protein Activities in Relation to Treatment Outcome in Acute Myeloid Leukemia
Clin. Cancer Res.,
August 1, 2000;
6(8):
3205 - 3214.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. V. Dahl, N. J. Lacayo, N. Brophy, K. Dunussi-Joannopoulos, H. J. Weinstein, M. Chang, B. I. Sikic, and R. J. Arceci
Mitoxantrone, Etoposide, and Cyclosporine Therapy in Pediatric Patients With Recurrent or Refractory Acute Myeloid Leukemia
J. Clin. Oncol.,
May 9, 2000;
18(9):
1867 - 1875.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pallis and N. Russell
P-glycoprotein plays a drug-efflux-independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modulation of a sphingomyelin-ceramide apoptotic pathway
Blood,
May 1, 2000;
95(9):
2897 - 2904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Lee, S. L. George, M. Caligiuri, T. P. Szatrowski, B. L. Powell, S. Lemke, R. K. Dodge, R. Smith, M. Baer, and C. A. Schiffer
Parallel Phase I Studies of Daunorubicin Given With Cytarabine and Etoposide With or Without the Multidrug Resistance Modulator PSC-833 in Previously Untreated Patients 60 Years of Age or Older With Acute Myeloid Leukemia: Results of Cancer and Leukemia Group B Study 9420
J. Clin. Oncol.,
September 1, 1999;
17(9):
2831 - 2831.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Advani, H. I. Saba, M. S. Tallman, J. M. Rowe, P. H. Wiernik, J. Ramek, K. Dugan, B. Lum, J. Villena, E. Davis, et al.
Treatment of Refractory and Relapsed Acute Myelogenous Leukemia With Combination Chemotherapy Plus the Multidrug Resistance Modulator PSC 833 (Valspodar)
Blood,
February 1, 1999;
93(3):
787 - 795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nakayama, M. Wada, T. Harada, J. Nagayama, H. Kusaba, K. Ohshima, M. Kozuru, H. Komatsu, R. Ueda, and M. Kuwano
Hypomethylation Status of CpG Sites at the Promoter Region and Overexpression of the Human MDR1 Gene in Acute Myeloid Leukemias
Blood,
December 1, 1998;
92(11):
4296 - 4307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Millard, E. Degrave, M. Philippe, and J.-L. Gala
Detection of intracellular antigens by flow cytometry: comparison of two chemical methods and microwave heating
Clin. Chem.,
November 1, 1998;
44(11):
2320 - 2330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Legrand, G. Simonin, J.-Y. Perrot, R. Zittoun, and J.-P. Marie
Pgp and MRP Activities Using Calcein-AM Are Prognostic Factors in Adult Acute Myeloid Leukemia Patients
Blood,
June 15, 1998;
91(12):
4480 - 4488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lau, S. Nightingale, G. P. Taylor, T. W. Gant, and A. J. Cann
Enhanced MDR1 Gene Expression in Human T-Cell Leukemia Virus-I-Infected Patients Offers New Prospects for Therapy
Blood,
April 1, 1998;
91(7):
2467 - 2474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Filipits, G. Pohl, T. Stranzl, R. W. Suchomel, R. J. Scheper, U. Jager, K. Geissler, K. Lechner, and R. Pirker
Expression of the Lung Resistance Protein Predicts Poor Outcome in De Novo Acute Myeloid Leukemia
Blood,
March 1, 1998;
91(5):
1508 - 1513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
