Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia

Kunadt, Desireé; Dransfeld, Christian; Dill, Claudia; Schmiedgen, Maria; Kramer, Michael; Altmann, Heidi; Röllig, Christoph; Bornhäuser, Martin; Mahlknecht, Ulrich; Schaich, Markus; Stölzel, Friedrich

doi:10.1007/s00277-020-04163-7

Cited by 15 publications

(9 citation statements)

References 31 publications

(33 reference statements)

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“…133 Three polymorphisms might predict the outcome of acute myeloid leukaemia, but any corresponding effect of these polymorphisms on transporter expression or function has so far not been established. 134…”

Section: [H3] Germline Mutations In Abcc1mentioning

confidence: 99%

The ATP-binding cassette proteins ABCB1 and ABCC1 as modulators of glucocorticoid action

et al. 2022

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Responses to hormones that act through nuclear receptors are controlled by modulating hormone concentrations not only in the circulation but also within target tissues. The role of enzymes that amplify or reduce local hormone concentrations has become well-established for glucocorticoid and other lipophilic hormones; moreover, transmembrane transporters have proven critical in determining tissue responses to thyroid hormones. However, there has been less consideration of the role of transmembrane transport for steroid hormones. ATP-binding cassette (ABC) proteins were first shown to influence the accumulation of glucocorticoids in cells almost three decades ago, but observations over the past ten years suggest that differential transport propensities of both exogenous and endogenous glucocorticoids by ABCB1 and ABCC1 transporters provides a mechanism whereby different tissues are preferentially sensitive to different steroids. This Review summarises this evidence and the new insights provided for the physiology and pharmacology of glucocorticoid action, including new approaches to glucocorticoid replacement.

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Section: [H3] Germline Mutations In Abcc1mentioning

confidence: 99%

The ATP-binding cassette proteins ABCB1 and ABCC1 as modulators of glucocorticoid action

et al. 2022

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“…In AML, drug resistance toward standard chemotherapeutic compounds is due to different factors, such as enhanced DNA repair, inhibition of cancer cell apoptosis, alteration of signaling pathways, alterations in drug metabolism enzymes, drug sequestration in intracellular organelles, and overexpression of efflux drug transporters [ 6 , 7 ]. In addition, overexpression of P-gp can lead to failure of the treatment or relapse.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, overexpression of P-gp can lead to failure of the treatment or relapse. In fact, P-gp overexpression can result in highly aggressive AML clones, which need more intensive treatment and invasive procedures [ 6 , 7 ]. Multidrug resistance mechanisms also produce resistance to microtubule-targeting agents [ 8 ], such as vinca alkaloids and taxanes.…”

Section: Introductionmentioning

confidence: 99%

Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients

Kanellou

Georgakopoulos-Soares

Zaravinos

2023

Cancers

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Acute myeloid leukemia (AML) is a heterogeneous and complex disease concerning molecular aberrations and prognosis. RUNX1/RUNX1T1 is a fusion oncogene that results from the chromosomal translocation t(8;21) and plays a crucial role in AML. However, its impact on the transcriptomic profile of different age groups of AML patients is not completely understood. Here, we investigated the deregulated gene expression (DEG) profiles in adult and pediatric RUNX1/RUNX1T1-positive AML patients, and compared their functions and regulatory networks. We retrospectively analyzed gene expression data from two independent Gene Expression Omnibus (GEO) datasets (GSE37642 and GSE75461) and computed their differentially expressed genes and upstream regulators, using limma, GEO2Enrichr, and X2K. For validation purposes, we used the TCGA-LAML (adult) and TARGET-AML (pediatric) patient cohorts. We also analyzed the protein–protein interaction (PPI) networks, as well as those composed of transcription factors (TF), intermediate proteins, and kinases foreseen to regulate the top deregulated genes in each group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were further performed for the DEGs in each dataset. We found that the top upregulated genes in (both adult and pediatric) RUNX1/RUNX1T1-positive AML patients are enriched in extracellular matrix organization, the cell projection membrane, filopodium membrane, and supramolecular fiber. Our data corroborate that RUNX1/RUNX1T1 reprograms a large transcriptional network to establish and maintain leukemia via intricate PPI interactions and kinase-driven phosphorylation events.

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“…For example, in acute myeloid leukemia (AML), drug resistance toward standard chemotherapeutic compounds, due to overexpression of P‐gp, leads to failure of the treatment or relapse. This P‐gp overexpression can result in highly aggressive AML clone, which needs more intensive treatment and invasive procedures (Kunadt et al, 2020; J. Zhang et al, 2019). MDR mechanisms produce resistance to microtubule‐targeting agents (Van Vuuren et al, 2015), such as Vinca alkaloids and Taxanes.…”

Section: Introductionmentioning

confidence: 99%

Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line

Labbozzetta

Barreca

Spanò

et al. 2022

Drug Development Research

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A series of [1,2]oxazolo [5,4-e]isoindole derivatives was evaluated against HL-60 cell line and its multidrug resistance (MDR) variant, HL-60R, resistant to doxorubicin and to other P-gp substrates by overexpressing the efflux pump. They displayed antiproliferative activities, with IC 50 values ranging from 0.02 to 5.5 µM. In particular, the newly synthesized compound 4k produced synergistic effects in terms of cell growth inhibition and cell death induction either in combination with a Vinca alkaloid, Vinblastine, and a Taxane, Paclitaxel in HL-60R cells. The study of the mechanism of action indicated that all compounds showed antimitotic activity through inhibition of tubulin polymerization. Thus, [1,2]oxazoles could represent a valuable tool to overcome MDR mechanism, confirming the potential use of this class of compounds.

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Multidrug-related protein 1 (MRP1) polymorphisms rs129081, rs212090, and rs212091 predict survival in normal karyotype acute myeloid leukemia

Cited by 15 publications

References 31 publications

The ATP-binding cassette proteins ABCB1 and ABCC1 as modulators of glucocorticoid action

The ATP-binding cassette proteins ABCB1 and ABCC1 as modulators of glucocorticoid action

Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients

Novel insights on [1,2]oxazolo[5,4‐e]isoindoles on multidrug resistant acute myeloid leukemia cell line

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