Upregulation of stem cell genes in multidrug resistant K562 leukemia cells

Lehne, Gustav; Grasmo-Wendler, Unn Hilde; Berner, Jeanne Marie; Meza‐Zepeda, Leonardo A.; Adamsen, Birgitte Lid; Flack, Aksel; Reiner, Andrew H.; Clausen, O. P. F.; Hovig, Eivind; Myklebost, Ola

doi:10.1016/j.leukres.2009.03.028

Cited by 24 publications

(17 citation statements)

References 48 publications

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“…Acaa2 was reported to be differentially expressed in CEM and drug-resistant leukemia cells [26]. Crot expression was found to be over-expressed in multidrug-resistant K562 leukemia cells [28]. In the current study, we found mRNA and protein levels of Acaa2, Aldh1l2, Acadvl, Echs1, and Hadha were significantly increased due to benzene exposure.…”

Section: Discussionsupporting

confidence: 56%

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Sun

Cao

Zhang

et al. 2016

IJERPH

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Abstract:Benzene is a well-known hematotoxic carcinogen that can cause leukemia and a variety of blood disorders. Our previous study indicated that benzene disturbs levels of metabolites in the fatty acid β-oxidation (FAO) pathway, which is crucial for the maintenance and function of hematopoietic and leukemic cells. The present research aims to investigate the effects of benzene on changes in the expression of key enzymes in the FAO pathway in male C3H/He mice. Results showed that benzene exposure caused reduced peripheral white blood cell (WBC), red blood cell (RBC), platelet (Pit) counts, and hemoglobin (Hgb) concentration. Investigation of the effects of benzene on the expression of FA transport-and β-oxidation-related enzymes showed that expression of proteins Cpt1a, Crat, Acaa2, Aldh1l2, Acadvl, Crot, Echs1, and Hadha was significantly increased. The ATP levels and mitochondrial membrane potential decreased in mice exposed to benzene. Meanwhile, reactive oxygen species (ROS), hydrogen peroxide (H 2 O 2 ), and malondialdehyde (MDA) levels were significantly increased in the benzene group. Our results indicate that benzene induces increased expression of FA transport and β-oxidation enzymes, mitochondrial dysfunction, and oxidative stress, which may play a role in benzene-induced hematotoxicity.

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Section: Discussionsupporting

confidence: 56%

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Sun

Cao

Zhang

et al. 2016

IJERPH

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“…In addition, ABCB5 gene silencing increases substantially the sensitivity of human melanoma cells to the anticancer chemotherapeutics 5-fluorouracil (5-FU) and camptothecin (112). A potential broader role for ABCB5 in anticancer chemotherapeutic resistance is suggested by the observation that across a panel of human cancer cell lines used by the National Cancer Institute for drug screening, ABCB5 gene expression levels correlate with chemoresistance to 45 of 119 anticancer agents (93), and the finding that human chronic myeloid leukemia cells resistant to the anticancer chemotherapeutic vincristine exhibit ABCB5 gene amplification and enhanced expression (113,114). These results warrant further in vivo examination to determine whether ABCB5-targeted sensitization to clinically relevant therapeutic agents represents a feasible and effective strategy to eradicate chemoresistant CSCs.…”

Section: Figurementioning

confidence: 99%

The therapeutic promise of the cancer stem cell concept

Frank¹,

Schatton²,

Frank³

2010

J. Clin. Invest.

565

486

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Cancer stem cells (CSCs) are a subpopulation of tumor cells that selectively possess tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of nontumorigenic cancer cell progeny through differentiation. As we discuss here, they have been prospectively identified in several human malignancies, and their relative abundance in clinical cancer specimens has been correlated with malignant disease progression in human patients. Furthermore, recent findings suggest that clinical cancer progression driven by CSCs may contribute to the failure of existing therapies to consistently eradicate malignant tumors. Therefore, CSC-directed therapeutic approaches might represent translationally relevant strategies to improve clinical cancer therapy, in particular for those malignancies that are currently refractory to conventional anticancer agents directed predominantly at tumor bulk populations.

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“…that development of drug resistance in a CML cell line results in ABCB5 gene amplification and mRNA overexpression and in the induction of stem cell genes raises the possibility that ABCB5 may serve similar chemoresistance functions in this malignancy, with potentially important implications should similar mechanisms be operative in drug-resistant clinical leukemias. (86,87) Since ABCB5 + CSC frequency also correlated significantly with clinical melanoma progression,(26) the ABCB5 marker identified a novel, direct link between CSC, cancer therapeutic resistance, and clinical neoplastic progression in a human malignancy.…”

Section: Cancer Stem Cell-mediated Resistance To Conventional Tumor Tmentioning

confidence: 99%

Identification and targeting of cancer stem cells

2009

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Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self-renewal and give rise to bulk populations of nontumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using markerspecific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and clinical tumor progression. Importantly, proof-of-principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC-targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC.

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Upregulation of stem cell genes in multidrug resistant K562 leukemia cells

Cited by 24 publications

References 48 publications

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

The therapeutic promise of the cancer stem cell concept

Identification and targeting of cancer stem cells

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