|
|
 Previous Article | Table of Contents | Next Article 
Predominance of functional multidrug resistance (MDR-1) phenotype in CD34+
acute myeloid leukemia cells
PA te Boekhorst, K de Leeuw, M Schoester, S Wittebol, K Nooter, A Hagemeijer, B Lowenberg and P Sonneveld
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
The expression of the MDR-1-encoded P-170 glycoprotein (P-170) associated
with clinical multidrug resistance (MDR) was investigated in 52 consecutive
patients with untreated acute myeloid leukemia (AML). P- 170 expression was
analyzed in correlation with CD34 expression and clinical response. Thirty
of 52 patients expressed P-170 (58%). Eight of 30 P-170+ as compared with
16 of 22 P-170- patients achieved a complete remission (CR) (27% v 73%, P =
.003). In 21 of 30 P-170+ patients, expression of the CD34 antigen was
observed in greater than 10% of the blast cells, as compared with 14 of 22
P-170- patients (70% v 64%, P > .05). The CR rate of CD34+ and CD34-
patients was 31% and 76%, respectively (P = .006). In AMLs that
simultaneously expressed both P-170 and CD34, the CR rate was worse as
compared with those negative for P-170 and CD34 (5% v 63%, P = .004). In 12
patients (8 P- 170+, 4 P-170-) CD34 and P-170 expression were further
characterized by double fluorescence studies. It was shown that P-170+
cells were largely, but not exclusively, restricted to the CD34+ cell
population. For the 8 P-170+ AML samples, the median ratio of P-170+/P-170-
in CD34+ cells was 4.845 (range, 0.60 to 25.00) as compared with 0.135
(range, 0.02 to 0.67) in CD34- cells. In these 12 AML samples, the presence
of functional resistance as defined by reduced daunorubicin accumulation
was evaluated in CD34+ and CD34- AML cells. In 8 of 8 P- 170+ patients,
intracellular daunorubicin accumulation in CD34+ AML blast cells was lower
than in CD34- cells, and it increased after cyclosporin addition. No
difference of intracellular daunorubicin accumulation was observed between
CD34+ and CD34- AML cells of 4 P-170- patients. These data indicate that
P-170 expression in AML with a heterogeneous CD34+ phenotype seems
predominantly present in CD34+ AML blast cells.
Volume 82,
Issue 10,
pp. 3157-3162,
11/15/1993
Copyright © 1993 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:
|
|
|
|
 
M. H.G.P. Raaijmakers, E. P.L.M. de Grouw, B. A. van der Reijden, T. J.M. de Witte, J. H. Jansen, and R. A.P. Raymakers
ABCB1 Modulation Does Not Circumvent Drug Extrusion from Primitive Leukemic Progenitor Cells and May Preferentially Target Residual Normal Cells in Acute Myelogenous Leukemia.
Clin. Cancer Res.,
June 1, 2006;
12(11):
3452 - 3458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. van der Holt, B. Lowenberg, A. K. Burnett, W. U. Knauf, J. Shepherd, P. P. Piccaluga, G. J. Ossenkoppele, G. E. G. Verhoef, A. Ferrant, M. Crump, et al.
The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis
Blood,
October 15, 2005;
106(8):
2646 - 2654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Kolitz, S. L. George, R. K. Dodge, D. D. Hurd, B. L. Powell, S. L. Allen, E. Velez-Garcia, J. O. Moore, T. C. Shea, E. Hoke, et al.
Dose Escalation Studies of Cytarabine, Daunorubicin, and Etoposide With and Without Multidrug Resistance Modulation With PSC-833 in Untreated Adults With Acute Myeloid Leukemia Younger Than 60 Years: Final Induction Results of Cancer and Leukemia Group B Study 9621
J. Clin. Oncol.,
November 1, 2004;
22(21):
4290 - 4301.
[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]
|
|
|
|
|
|
|
S. L. A. Plasschaert, D. M. van der Kolk, E. S. J. M. de Bont, W. A. Kamps, K. Morisaki, S. E. Bates, G. L. Scheffer, R. J. Scheper, E. Vellenga, and E. G. E. de Vries
The Role of Breast Cancer Resistance Protein in Acute Lymphoblastic Leukemia
Clin. Cancer Res.,
November 1, 2003;
9(14):
5171 - 5177.
[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]
|
|
|
|
|
|
|
D. M. van der Kolk, E. Vellenga, G. L. Scheffer, M. Muller, S. E. Bates, R. J. Scheper, and E. G. E. de Vries
Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia
Blood,
May 15, 2002;
99(10):
3763 - 3770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Baer, C. C. Stewart, R. K. Dodge, G. Leget, N. Sule, K. Mrozek, C. A. Schiffer, B. L. Powell, J. E. Kolitz, J. O. Moore, et al.
High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361)
Blood,
June 1, 2001;
97(11):
3574 - 3580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Legrand, J.-Y. Perrot, M. Baudard, A. Cordier, R. Lautier, G. Simonin, R. Zittoun, N. Casadevall, and J.-P. Marie
The immunophenotype of 177 adults with acute myeloid leukemia: proposal of a prognostic score
Blood,
August 1, 2000;
96(3):
870 - 877.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
C. D. Jennings and K. A. Foon
Recent Advances in Flow Cytometry: Application to the Diagnosis of Hematologic Malignancy
Blood,
October 15, 1997;
90(8):
2863 - 2892.
[Full Text]
[PDF]
|
|
|
|
|
