The clinical relevance and prognostic significance of adenosine triphosphate ATP-binding cassette (ABCB5) and multidrug resistance (MDR1) genes expression in acute leukemia: an Egyptian study

Farawela, Hala M.; Khorshied, Mervat M.; Kassem, Neemat; Kassem, Heba A.; Zawam, Hamdy

doi:10.1007/s00432-014-1694-3

Cited by 24 publications

(27 citation statements)

References 35 publications

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“…After induction chemotherapy, we found that the more ABC transporters were overexpressed in de devo AML patients, the less chances the patients had of achieving CR. Researchers suggested this phenomenon occurs due to multifactorial regulation, leading to the reduction of intracellular drug concentrations through modulations in drug influx and efflux (12). In addition, previous study proposed that children with AML who expressed more ABC transporters had a lower chance to respond well to therapy (as measured by the percentage of patient having <5% leukemic cells by day 15 of therapy) (18).…”

Section: Discussionmentioning

confidence: 99%

“…Non-remission (NR) was defined as a marrow blasts percentage did not decrease to 25% or below after induction chemotherapy. Early death was defined as death before completion of the induction chemotherapy cycle (12). The patients who reached CR and maintained relapse free survivals (RFS) for >9 months were regarded as good response to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia

Liu

Gong

et al. 2018

Oncol Lett

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Abstract. Chemotherapy failure remains a challenge when treating patients with acute myeloid leukemia (AML), who often suffer from persistent or relapsed disease. The multidrug resistance (MDR) mediated by efflux transporters of the ATP binding cassette (ABC) superfamily is a major obstacle for successful chemotherapy. The present study aimed to elucidate whether the expression of ABC transporters was associated with prognostic factors and responses to chemotherapy in patients with AML, with particular focus on whether co-expression of multiple ABC transporters resulted in a worse prognosis. In the present study, the mRNA expression levels of ABC transporters ABCB1, ABCB4, ABCC1, ABCC4 and ABCG2 in bone marrow (BM) mononuclear cell (MNC) samples from 96 de novo patients with AML and in the peripheral blood (PB) MNC samples from 22 normal individuals were investigated using reverse transcription-quantitative polymerase chain reaction analysis. It was revealed that ABCB1, ABCC1, ABCC4 and ABCG2 were expressed at higher levels in patients with AML compared with normal individuals, whereas ABCB4 had a lower expression level. The expression of ABCB4 in patients with AML was significantly lower than in normal individuals (P<0.001). Patients risk status was associated with ABCB1 (P= 0.037), ABCC1 (P= 0.047), ABCC4 (P=0.015) and ABCG2 (P=0.027). The 4 genes were expressed a significantly higher levels in the poor response group compared with the good response group (ABCB1, P= 0.014; ABCC1, P= 0.021; ABCC4, P= 0.005; ABCG2, P= 0.009). The overexpression of the 4 ABC transporters and the complete remission rate were inversely correlated (P<0.001). These results suggest that the co-expression of multiple ABC transporters may contribute to a worse prognosis in AML.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia

Liu

Gong

et al. 2018

Oncol Lett

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“…[5] All these results indicated that, ABCB5 expression is closely related to the CSCs-driven cancer, [41,65,67] ABCB5 expressing or not in CRC may represent another drug-resistant mechanism. [68] Therapies target CR-CSCs subpopulation with tumorigenicity and chemotherapy resistance can improve the therapy efficacy in these malignant tumors. [41] Some research suggested that CSC is resistant to radiotherapy, such as, compared with CD133 − tumor cell, the chemotherapy resistance increased in CD133 + human brain glioma stem cell, meanwhile, CD133 + tumor cells presented preferentially activation of DNA damage checkpoint in response to radiotherapy-induced DNA damage and repair.…”

Section: Drug-resistance Of Colorectal Cancer Stem Cellsmentioning

confidence: 99%

Updates in colorectal cancer stem cell research

Xue-qian

Fan

2014

J Can Res Ther

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Colorectal cancer (CRC) is one of the world most common malignant tumors, also is the main disease, which cause tumor-associated death. Surgery and chemotherapy are the most used treatment of CRC. Recent research reported that, cancer stem cells (CSCs) are considered as the origin of tumor genesis, development, metastasis and recurrence in theory. At present, it has been proved that, CSCs existed in many tumors including CRC. In this review, we summary the identification of CSCs according to the cell surface markers, and the development of drugs that target colorectal cancer stem cells.

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“…90 Although the underlying basis for susceptibility is uncertain, analysis of potential glioma susceptibility loci by GWAS has identified variants in chromosome 9p21 near CDKN2A and CDKN2B. 91,92 The glioma candidates are not in the same linkage disequilibrium block as the CDKN2A melanoma gene, but it suggests the possibility that this region may account for shared predisposition to both cancers.…”

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confidence: 99%

“…[89][90][91] A possible role has also been proposed in oral SCC and leukaemia, and it is overexpressed in almost a third of sporadic oesophageal cancer. 21,92,93 The rare segregating variant in this family (rs193255587) is a splicing mutation, and the effects of this mutation would depend on consequent protein expression and function. Figure 16).…”

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confidence: 99%

Familial melanoma risk genes in Queensland

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Melanoma 'risk' is multifaceted, with genetic, phenotypic, and environmental factors all contributing to melanoma predisposition. Although the majority of melanoma is attributable to random acquired mutations in melanocytes, a positive family history is associated with an increased risk of developing the disease, and the presence of heritable germline variants is an important component of melanoma susceptibility for some families. Mutation in one of the known high penetrance melanoma predisposition genes, comprising CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP, and TERT, underpins melanoma risk for approximately half of all high-density familial clustering of melanoma. However, the underlying genetic basis of disease remains unexplained for many families.It is likely that a polygenic component to melanoma predisposition accounts for the remainder of families, where overall susceptibility is influenced by combinations of low to moderate risk polymorphisms, rare high penetrance germline mutations, and modulation of risk by environmental and genetic factors. Although no single presently known germline alteration guarantees disease development, the main impact of predisposition genes is the elevation of baseline melanoma risk.For an individual with existing genetic susceptibility, it is likely that fewer sporadic mutations are required to accumulate before a critical level for oncogenesis is reached. Beyond conferring risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to diverse cancer phenotypes. Familial risk has been proposed as a shared feature of many cancers, and clustering of additional cancers in melanoma families has been observed at rates greater than expected by chance.In a cohort of 178 'intermediate risk' melanoma families, cancer development was assessed over a 33 year period, and identified significantly more than expected bladder cancer, lymphoid leukaemia, and myeloma. Further to population level cancer risk, it is proposed that some cancer dense families carry known and possibly as-yet-unidentified melanoma predisposition genes.Eight families with high melanoma case density and eleven individuals with three or more invasive cancer types including melanoma were selected for further follow up with whole exome or whole genome sequencing. Multiple damaging variants in cancer-associated genes were identified, supporting a polygenic basis for melanoma susceptibility. Given the diversity of genetic variants and other cancer types in the cohort, it is possible that some cancer-associated genes identified here also have pleiotropic effects in predisposing to melanoma.iii

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The clinical relevance and prognostic significance of adenosine triphosphate ATP-binding cassette (ABCB5) and multidrug resistance (MDR1) genes expression in acute leukemia: an Egyptian study

Abstract: In conclusion, the results obtained by the current study provide additional evidence of the role played by these genes as predictive factors for resistance of leukemic cells to chemotherapy and hence treatment outcome.

Cited by 24 publications

References 35 publications

Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia

Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia

Updates in colorectal cancer stem cell research

Familial melanoma risk genes in Queensland

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