Single-cell analysis of K562 cells: An imatinib-resistant subpopulation is adherent and has upregulated expression of BCR-ABL mRNA and protein

Karimiani, Ehsan Ghayoor; Marriage, Fiona; Merritt, Anita J.; Burthem, John; Byers, Richard; Day, Philip J.

doi:10.1016/j.exphem.2013.11.006

Cited by 21 publications

(14 citation statements)

References 29 publications

(53 reference statements)

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“…The procedures were performed as described previously with some modifications. 4,7 The raw liposuctioned aspirate was washed extensively with D-Hanks solution to remove contaminating blood and local anesthetics. The cells were washed two times and plated in T-75 tissue culture flasks at a density of 2 × 10 6 ml − 1 .…”

Section: Preparation Of Cancer Stem Cells From CMLmentioning

confidence: 99%

“…3 Allogeneic bone marrow transplantation, the only curative treatment for CML, is associated with substantial morbidity and mortality and is limited to patients for whom a suitable donor is available. 4,5 The mechanisms favoring the growth advantage of Philadelphia chromosome-positive cells over normal cells in CML are not fully elucidated but could be partly because of altered apoptosis and longer survival of CML clones. 6,7 Also, little is known about the biologic characteristics of disease progression in CML.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

et al. 2015

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The p53 mutation in chronic myeloid leukemia (CML) led to decreased overall survival and therapy resistance which was also closely correlated with the downstream proto-oncogenes BCL-2, TCL-1 and MCL-1. We in this study aimed to investigate the function of miR130a in p53 tumor suppressor signaling pathway. We performed microRNA (miRNA) expression profile analysis in CML cancer stem cells of 38 cases and extracted total RNA from peripheral blood of 143 cases. Standard curves of U6 and miRNA were made from 10-fold serial dilutions of the cDNA, which were quantified using real-time quantitative PCR with SYBR Green by ABI 7300. The p53 mutations and BCR/ABL mutation status analysis in CML patients were detected by PCR and direct sequencing. Candidate targets of miR130a of putative relevance in CML pathogenesis were analyzed by bioinformatics approach. We then used dual-luciferase activity assay to verify the target genes of miR130a and used western blot analysis to elucidate the mechanism of miR130a on modulating drug resistance. The levels of miR-130a expression in CML were significantly lower in poor prognostic subgroups, defined by prognostic factors including mutated BCR/ABL status, p53 and ATM deletions and p53 mutations. Furthermore, underexpression of miR-130a was significantly associated with shorter overall survival and treatment-free survival in CML patients. We demonstrated that miR130a function as tumor suppressors by inhibiting multiple anti-apoptosis proteins, including BCL-2, MCL-1 and XIAP. This was a direct effect because miR130a negatively regulated expression of a BCL-2/MCL-1/XIAP 3'untranslated region-based reporter construct. Transfection of miR130a mimics into CML cells from 30 patients without p53 aberrations led to significant increases in apoptosis compared with transfection with the miRNA control. Besides, enforced expression of miR130a had no significant drug-sensitization effect in CML cells from p53-attenuated patients. MiR-130a may have an important role in the pathogenesis of CML and may be useful for assessing prognosis in patients with CML. Moreover, miR130a may provide a possible therapeutic avenue and a sensitive indicator of the activity of the p53 in CML.

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Section: Preparation Of Cancer Stem Cells From CMLmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

et al. 2015

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“…miRNAs are known to play important roles in the regulation of cell growth [ 19 ], proliferation [ 20 ], apoptosis [ 21 ], survival, and signal transduction [ 22 ]. Recent studies have suggested that miRNAs are also involved in cancer development and are thus important for the diagnosis, treatment, and prognosis of the disease [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

miRNA143 Induces K562 Cell Apoptosis Through Downregulating BCR-ABL

et al. 2016

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BackgroundLeukemia seriously threats human health and life. MicroRNA regulates cell growth, proliferation, apoptosis, and cell cycle. Whether microRNA could be treated as a target for leukemia is still unclear and the mechanism by which microRNA143 regulates K562 cells needs further investigation.Material/MethodsmiRNA143 and its scramble miRNA were synthesized and transfected to K562 cells. MTT assay was used to detect K562 cell proliferation. Flow cytometry and a caspase-3 activity detection kit were used to test K562 cell apoptosis. Western blot analysis was performed to determine breakpoint cluster region-Abelson (BCR-ABL) expression. BCR-ABL overexpression and siRNA were used to change BCR-ABL level, and cell apoptosis was detected again after lipofection transfection.ResultsmiRNA143 transfection inhibited K562 cell growth and induced its apoptosis. miRNA143 transfection decreased BCR-ABL expression. BCR-ABL overexpression suppressed miRNA143-induced K562 cell apoptosis, while its reduction enhanced miRNA143-induced apoptosis.ConclusionsmiRNA143 induced K562 cell apoptosis through downregulating BCR-ABL. miRNA143 might be a target for a new leukemia therapy.

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“… 9 , 10 While 5-years overall survival rate of CML patients without imatinib was recorded as 24%, it increased gradually to 39% (1966-1998) and 56.8% (1999-2006) and the overall survival was estimated to 85% with the application of imatinib. 2 , 11 , 12 Simultaneously during treatment, the development of resistance in many leukemia patients in the chronic phase 8 , 13 , 14 and accelerated/ blast crisis phase 8 limits the use of tyrosine kinase inhibitors. The phenomenon of resistance against the chemotherapeutic agents called chemoresistance or multidrug resistance (MDR).…”

Section: Introductionmentioning

confidence: 99%

Role of membrane-embedded drug efflux ABC transporters in the cancer chemotherapy

et al. 2020

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One of the major problems being faced by researchers and clinicians in leukemic treatment is the development of multidrug resistance (MDR) which restrict the action of several tyrosine kinase inhibitors (TKIs). MDR is a major obstacle to the success of cancer chemotherapy. The mechanism of MDR involves active drug efflux transport of ABC superfamily of proteins such as Pglycoprotein (P-gp/ABCB1), multidrug resistance-associated protein 2 (MRP2/ABCC2), and breast cancer resistance protein (BCRP/ABCG2) that weaken the effectiveness of chemotherapeutics and negative impact on the future of anticancer therapy. In this review, the authors aim to provide an overview of various multidrug resistance (MDR) mechanisms observed in cancer cells as well as the various strategies developed to overcome these MDR. Extensive studies have been carried out since last several years to enhance the efficacy of chemotherapy by defeating these MDR mechanisms with the use of novel anticancer drugs that could escape from the efflux reaction, MDR modulators or chemosensitizers, multifunctional nanotechnology, and RNA interference (RNAi) therapy.

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Single-cell analysis of K562 cells: An imatinib-resistant subpopulation is adherent and has upregulated expression of BCR-ABL mRNA and protein

Cited by 21 publications

References 29 publications

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

miRNA143 Induces K562 Cell Apoptosis Through Downregulating BCR-ABL

Role of membrane-embedded drug efflux ABC transporters in the cancer chemotherapy

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