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Expression data at drug-sensitive and drug-resistant phases of canine B-cell lymphoma

ABSTRACT: Multidrug resistance (MDR) is one of the major obstacles during the chemotherapy in lymphoma patients. Although there have been various molecules associated with acquisition of MDR phenotype in human tumor cells, MDR of tumor cells have not been successfully overcome. Canine lymphoma is thought to be a spontaneous animal model of human lymphoma because it shares many similarities with human non-Hodgkin’s lymphoma. We conducted a comprehensive analysis of changes in gene expression profiles of canine lymphoma cells by microarray analysis using tumor cell samples at drug-sensitive and drug-resistant phases in 6 dogs. It was revealed that expression of the molecules related to chemotaxis and inflammation were down regulated in MDR phases.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE83274 | GEO | 2017/04/01

SECONDARY ACCESSION(S): PRJNA325465

REPOSITORIES: GEO

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Project description:The identification of multidrug resistant (MDR), extensively and totally drug resistant Mycobacterium tuberculosis (Mtb), in vulnerable sites such as Mumbai, is a grave threat to the control of tuberculosis. The current study aimed at explaining the rapid expression of MDR in Directly Observed Treatment Short Course (DOTS) compliant patients, represents the first study comparing global transcriptional profiles of 3 pairs of clinical Mtb isolates, collected longitudinally at initiation and completion of DOTS. While the isolates were drug susceptible (DS) at onset and MDR at completion of DOTS, they exhibited identical DNA fingerprints at both points of collection. The whole genome transcriptional analysis was performed using total RNA from H37Rv and 3 locally predominant spoligotypes viz. MANU1, CAS and Beijing, hybridized on MTBv3 (BuG@S) microarray, and yielded 36, 98 and 45 differentially expressed genes respectively. Genes encoding transcription factors (sig, rpoB), cell wall biosynthesis (emb genes), protein synthesis (rpl) and additional central metabolic pathways (ppdK, pknH, pfkB) were found to be down regulated in the MDR isolates as compared to the DS isolate of the same genotype. Up regulation of drug efflux pumps, ABC transporters, trans-membrane proteins and stress response transcriptional factors (whiB) in the MDR isolates was observed. The data indicated that Mtb, without specific mutations in drug target genes may persist in the host due to additional mechanisms like drug efflux pumps and lowered rate of metabolism. Furthermore this population of Mtb, which also showed reduced DNA repair activity, would result in selection and stabilization of spontaneous mutations in drug target genes, causing selection of a MDR strain in the presence of drug pressures. Efflux pump such as drrA may play a significant role in increasing fitness of low level drug resistant cells and assist in survival of Mtb till acquisition of drug resistant mutations with least fitness cost. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-134]

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Expression data at drug-sensitive and drug-resistant phases of canine B-cell lymphoma

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