Microarray analysis showed that PARP1 and CHE1 were constitutively expressed in CLL and had a high degree of correlation with each other and with TP53.
MDR1 RNA transcripts were independent of age, treatment status of the patients and the clinical stage of CLL, but correlated with the white blood cell count and MDR2 RNA transcripts.
In this study, we attempted to evaluate the apoptotic effects of the BPs pamidronate (PAM) and zoledronic acid (ZOL) in chronic lymphocytic leukemia (CLL) samples, and to correlate it with clinical parameters and multidrug resistance (MDR) phenotype (P-glycoprotein and multidrug resistance-related protein expression and/or their functional activity).
Correlation of bcl-2 with P-glycoprotein expression in chronic lymphocytic leukaemia and other haematological neoplasms but of neither marker with ex vivo chemosensitivity or patient survival.
This study was designed to investigate whether associations exist between expression of MDR-1 and MDR-3 P-gp and other markers of poor prognosis and/or prior exposure to therapeutic agents in chronic lymphocytic leukemia (CLL).
APO866 and Pgp inhibitors show a strong synergistic cooperation in leukemia cells, including acute myelogenous leukemia (AML) and B-cell chronic lymphocytic leukemia (B-CLL) samples.
68 CLL/NHL patients were analysed using flow cytometry with MDR1 and MRP specific antibodies and were divided into subgroups, untreated (n = 31). treated with non P-gp transportable drugs (n = 26), those treated with low total doses of P-gp transportable drugs (n = 6) and patients treated with high total doses of P-gp transportable drugs (n = 5).
We conclude that the level of expression of the MDR 1 gene in CLL is generally low, that the removal of granulocytes is important in studies of expression of MDR 1 mRNA in CLL, and that differential PCR provides a rapid and reliable method for quantifying the amount of a specific mRNA, even in very small samples of total RNA.
These findings suggest that P-glycoprotein overexpression in B-CLL is intrinsic rather than acquired and that P-glycoprotein activity is enhanced after exposure to multidrug resistance-associated drugs.
In conclusion, our results do not support a major influence of MDR1 variants on the risk of CLL, and these genomic polymorphisms are not associated with clinical prognostic factors in Chinese patients with CLL.
In conjunction with genetic abnormalities developing in B-cell progenitors, presumably expressing P glycoprotein (Pgp+), we postulate that developmentally altered T-cell descendants, along with quantitative imbalance among CD4+, their subsets and CD8+ lymphocytes in the peripheral blood, play an important additional role in facilitating the malignant B-cell clone emergence and in modulating the CLL clinical evolution.
We have studied the expression of this p-glycoprotein in chronic lymphatic leukaemia measured by immunofluorescence using a monoclonal antibody MRK 16 by flow cytometry.
The accumulation and cytotoxicity of vincristine (Vcr), etoposide (VP16), and daunorubicin (Dau) and effect of the resistance modifiers (RM) verapamil (Ver; 10 microM) and cyclosporin A (CyA; 3 microM) were studied in isolated rat cardiac myocytes, peripheral lymphocytes from seven patients with chronic lymphocytic leukemia (CLL), in the human leukemic cell line K562 and its two Vcr resistant mdr1 gene expressing sublines, K562/Vcr30, K562/Vcr150.
Etoposide-induced DNA strand breaks in relation to p-glycoprotein and topoisomerase II protein expression in leukaemic cells from patients with AML and CLL.
Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven).
Increased mdr1/P-glycoprotein mRNA levels were also found in relapsed state acute myelogenous leukaemias (AML), and in chronic lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for several years.
To investigate the potential role of MDR and transforming growth factor-beta (TFG-beta), a potent growth inhibitor of B lymphocytes, in the development of chemotherapeutic resistance in CLL, we evaluated 22 CLL patients for loss or mutation of TGF-beta receptors (TbetaR), plasma TGF-beta1 levels, and expression of MDR1 mRNA.
Multidrug resistance (MDR) was investigated in peripheral blood cells isolated from 40 patients with B cell chronic lymphocytic leukemia (B-CLL) and from 7 healthy volunteers, using a flow cytometric assay that detects cellular efflux of the fluorescent dye rhodamine 123 (Rh 123), which has been demonstrated to be transported from the cell by the P-glycoprotein pump.
Relationship between advanced oxidation protein products, advanced glycation end products, and S-nitrosylated proteins with biological risk and MDR-1 polymorphisms in patients affected by B-chronic lymphocytic leukemia.