The pattern of gene expression and gene dose profiles of 6-Mercaptopurine- and 6-Thioguanine-resistant human leukemia cells

Karim, Hazhar; Hashemi, Jamileh; Moshfegh, Ali; Fotoohi, Alan; Albertioni, Freidoun

doi:10.1016/j.bbrc.2011.06.120

Cited by 13 publications

(10 citation statements)

References 85 publications

(131 reference statements)

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“…3A), all of which have been previously associated with B cell lineage ALL and B cell activation and/or differentiation [31][32][33][34][35][36][37][38]. Their differential regulation upon MondoA knockdown was entirely confirmed on RNA or protein level by qRT-PCR or flow cytometry (Fig.…”

Section: Mondoa Knockdown Promotes Differentiation Of Leukemia Cellsmentioning

confidence: 70%

“…DNTT (terminal deoxynucleotidyltransterase) is expressed in normal and malignant pre-B and pre-T lymphocytes during early differentiation and contributes to the generation of antigen-receptor diversity [43]. In addition, DNTT has a strong anti-apoptotic function as its overexpression may contribute to resistance of leukemia cells to thiopurine-based chemotherapeutics [32]. Accordingly, downregulation of DNTT by MondoA knockdown may in part explain the increased cell death in our model.…”

Section: Discussionmentioning

confidence: 86%

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MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival

Wernicke¹,

Richter²,

Beinvogl³

et al. 2012

Leukemia Research

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Section: Mondoa Knockdown Promotes Differentiation Of Leukemia Cellsmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 86%

MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival

Wernicke¹,

Richter²,

Beinvogl³

et al. 2012

Leukemia Research

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“…The mechanism remains unclear but may be due to decreased synthesis of ATP, which will reduce GMPS activity. Furthermore, cells exhibiting reduced expression future science group Review Blaker, Arenas-Hernandez, Marinaki & Sanderson of GMPS appear resistant to MP [178]. These data support a role for genetic variation in GMPS to explain treatment nonresponse to AZA/MP, however in vivo studies are currently lacking.…”

Section: Genetic Factors Affecting Thiopurine Metabolismmentioning

confidence: 84%

The Pharmacogenetic Basis of Individual Variation in Thiopurine Metabolism

Blaker

Arenas-Hernandez

Sanderson

2012

Personalized Medicine

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Thiopurines are an important class of immunosuppressive therapy, which have been used in clinical practice for over 50 years. Despite this extensive experience many of the pharmacodynamic and pharmacokinetic properties of these drugs remain unknown. As a consequence there is often no clear explanation for the individual variation in response to treatment, both in terms of efficacy or adverse drug reactions. This review, which emphasizes practice in gastroenterology, summarizes the current understanding of thiopurine drug metabolism and highlights the role of nongenetic and genetic factors other than TPMT, which should be a focus for future research. Correlation of polymorphic variations in these genes with clinical outcomes is expected to clarify the basis for interindividual differences in thiopurine metabolism and enable a more personalized approach to therapy.

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“…In recent years, 6-thioguanine, a drug with anti-inflammatory, anticancer, and antiviral functions, has attracted increasing interest in pharmacology, medicine, and chemistry (Almer, Hjortswang, and Hindorf 2009;Brem, Daehn, and Karran 2011;Karim et al 2011;Ock et al 2012). The interaction between 6-thioguanine and proteins has been investigated by different methods (Qu et al 2009;Hui et al 2013;Xin et al 2013).…”

Section: Introductionmentioning

confidence: 97%

Characterization of the Interaction of 6-Thioguanine with Human Serum Albumin by Surface-Enhanced Raman Scattering and Molecular Modeling

Zhang

2015

Analytical Letters

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The interaction of 6-thioguanine and human serum albumin was investigated by fluorescence, ultraviolet-visible absorption, and surface-enhanced Raman scattering. The fluorescence of human serum albumin decreased with the concentration of 6-thioguanine, and the fluorescence quenching Downloaded by [New York University] at 10:14 29 May 20152 of human serum albumin by 6-thioguanine was static. Molecular modeling showed that 6-thioguanine was located in the hydrophobic cavity in subdomain IIA of human serum albumin.Surface-enhanced Raman scattering was combined with density function theory to characterize the orientation of 6-thioguanine on gold and the 6-thioguanine functional groups bonded to human serum albumin. 6-Thioguanine was shown to be tilted on the gold surface by a N-C=S moiety. The binding sites of 6-thioguanine to human serum albumin were the NH and amino groups of the pyrimidine ring of 6-thioguanine. This study may provide information regarding the metabolism of anticancer pharmaceuticals in the human body and assist in the development of efffective compounds.

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The pattern of gene expression and gene dose profiles of 6-Mercaptopurine- and 6-Thioguanine-resistant human leukemia cells

Cited by 13 publications

References 85 publications

MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival

MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival

The Pharmacogenetic Basis of Individual Variation in Thiopurine Metabolism

Characterization of the Interaction of 6-Thioguanine with Human Serum Albumin by Surface-Enhanced Raman Scattering and Molecular Modeling

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