Comparison of <i>BCR–ABL</i> Transcript Variants Between Patients With Chronic Myeloid Leukaemia and Leukaemia Cell Lines

Sales, Lívia de Oliveira; Mesquita, Felipe Pantoja; Portilho, Adrhyann Jullyanne de Sousa; Filho, Manoel Odorico de Moraes; Moraes, Maria Elisabete Amaral de; Montenegro, Raquel Carvalho; Moreira-Nunes, Caroline Aquino

doi:10.21873/invivo.11581

Cited by 3 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, a study previously carried out by our research group showed that the expression of BCR-ABL1 levels between leukemic cell lines, including K-562, and patients with CML was similar. This validates the use of these cell lines as an indispensable tool for the knowledge of the particularities related to the development, differentiation, and susceptibility to the treatment of tumor cells (33).…”

Section: Discussionsupporting

confidence: 65%

Combined Therapy of ATRA and Imatinib Mesylate Decreases BCR-ABL and ABCB1/MDR1 Expression Through Cellular Differentiation in a Chronic Myeloid Leukemia Model

Pinto

Portilho

Barbosa

et al. 2021

In Vivo

Self Cite

View full text Add to dashboard Cite

Background/Aim: Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease, and a major challenge for the eradication of CML is to understand the cause of the permanence of minimal residual disease (DRM). This work aimed to induce the maturation of leukemic stem cells with All-trans-retinoic acid (ATRA), making them sensitive to treatment with Imatinib (IM). Materials and Methods: K562 cells were treated with IM and with the combined therapy of ATRA together with IM for 48 and 72 h. The expression of BCR-ABL gene and multidrug resistance gene ABCB1 were evaluated using RT-qPCR. Results: The combined ATRA and IM therapy showed a discreet cell differentiation pattern, evidenced by the panoptic morphology analysis at 48 and 72 h of treatment. The BCR-ABL expression showed no statistical difference when treated alone with IM, however in combination with ATRA, the expression was statistically significant in 48 and 72 h (p≤0.0001) and when the treatment groups were compared to each other (p≤0.001). The ABCB1 gene expression showed a decrease in isolated IM therapy (p≤0.05) and in the combination in 48 and 72 h (p≤0.0001). Conclusion: Combined ATRA and IM therapy was shown to be effective in decreasing BCR-ABL and ABCB1 genes, possibly through the differentiation of blast cells, demonstrating that the therapy could be potentially effective in the blast crisis of the disease and for those patients who develop resistance to available CML treatments.

show abstract

Section: Discussionsupporting

confidence: 65%

Combined Therapy of ATRA and Imatinib Mesylate Decreases BCR-ABL and ABCB1/MDR1 Expression Through Cellular Differentiation in a Chronic Myeloid Leukemia Model

Pinto

Portilho

Barbosa

et al. 2021

In Vivo

Self Cite

View full text Add to dashboard Cite

show abstract

“…We additionally found that LXR‐mediated effects on CML cell behavior were dependent upon lipoproteins present in culture. These findings were demonstrated in K562 cells—one of the most well characterized CML cell lines that has been relatively understudied in regards to lipid metabolism (Clarke and Holyoake, 2017; De Oliveira et al, 2019). Together, these findings may have important implications for the progression and treatment of hematologic malignancies, as well as regulatory pathways of hematopoietic cells (Bovenga et al, 2015; Yvan‐Charvet et al, 2010).…”

Section: Discussionmentioning

confidence: 88%

“…These findings were demonstrated in K562 cells-one of the most well characterized CML cell lines that has been relatively understudied in regards to lipid metabolism (a-c) K562 cells were cultured with LDL (50 μg/mL), HDL (50 μg/mL), apoA1 (25 μg/mL), SAA-rich HDL (10 μg/mL) in the absence or presence of 5 μM TO901317 for 72 h. mRNA expression of (a) γglobin, (b) ALAS2, and (c) ITGA2B was determined by qPCR data, where data were normalized TO mRNA expression of GAPDH. Values with different letters at a given timepoint are significantly different (P < 0.05), *P = 0.035: HDL vs. SAA-rich HDL, n = 3 per treatment group (Clarke and Holyoake, 2017;De Oliveira et al, 2019). Together, these findings may have important implications for the progression and treatment of hematologic malignancies, as well as regulatory pathways of hematopoietic cells (Bovenga et al, 2015;Yvan-Charvet et al, 2010).…”

Section: Discussionmentioning

confidence: 92%

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Andersen

Dupree

Murray

et al. 2020

Lipids

View full text Add to dashboard Cite

Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human-derived low-density lipoproteins (LDL), highdensity lipoproteins (HDL), and HDL-associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells-a bone marrow-derived, stem-like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein-mediated effects were altered by concomitant LXR activation. We observed that LDL promoted higher K562 cell viability in a dose-and time-dependent manner and increased cellular cholesterol concentrations, while LXR activation by the agonist TO901317 ablated these effects. LXR activation in the presence of HDL, apoA1 and SAA-rich HDL suppressed K562 cell viability, while robustly inducing mRNA expression of ATP-binding cassette transporter A1 (ABCA1). HDL and its associated proteins additionally suppressed mRNA expression of anti-apoptotic B-cell lymphoma-extra large (BCL-xL), and the erythroid lineage marker 5 0-aminolevulinate synthase 2 (ALAS2), while SAA-rich HDL induced mRNA expression of the megakaryocytic lineage marker integrin subunit alpha 2b (ITGA2B). Together, these findings suggest that lipoproteins and LXR may impact the viability and characteristics of CML cells.

show abstract

1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation of H2AFX in Leukemia Multidrug Resistant Cell Line

Portilho

Silva

Bezerra

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

The multidrug resistance (MDR) phenotype is one of the major obstacles in the treatment of chronic myeloid leukemia (CML) in advantage stages such as blast crisis. In this scenario, more patients develop resistance mechanisms during the course of the disease, making tyrosine kinase inhibitors (TKIs) target therapies ineffective. Therefore, the aim of the study was to examine the pharmacological role of CNN1, a para-naphthoquinone, in a leukemia multidrug resistant cell line. First, the in vitro cytotoxic activity of Imatinib Mesylate (IM) in K-562 and FEPS cell lines was evaluated. Subsequently, membrane integrity and mitochondrial membrane potential assays were performed to assess the cytotoxic effects of CNN1 in K-562 and FEPS cell lines, followed by cell cycle, alkaline comet assay and annexin V-Alexa Fluor® 488/propidium iodide assays (Annexin/PI) using flow cytometry. RT-qPCR was used to evaluate the H2AFX gene expression. The results demonstrate that CNN1 was able to induce apoptosis, cell membrane rupture and mitochondrial membrane depolarization in leukemia cell lines. In addition, CNN1 also induced genotoxic effects and caused DNA fragmentation, cell cycle arrest at the G2/M phase in leukemia cells. No genotoxicity was observed on peripheral blood mononuclear cells (PBMC). Additionally, CNN1 increased mRNA levels of H2AFX. Therefore, CNN1 presented anticancer properties against leukemia multidrug resistant cell line being a potential anticancer agent for the treatment of resistant CML.

show abstract

Comparison of BCR–ABL Transcript Variants Between Patients With Chronic Myeloid Leukaemia and Leukaemia Cell Lines

Cited by 3 publications

References 35 publications

Combined Therapy of ATRA and Imatinib Mesylate Decreases BCR-ABL and ABCB1/MDR1 Expression Through Cellular Differentiation in a Chronic Myeloid Leukemia Model

Combined Therapy of ATRA and Imatinib Mesylate Decreases BCR-ABL and ABCB1/MDR1 Expression Through Cellular Differentiation in a Chronic Myeloid Leukemia Model

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation of H2AFX in Leukemia Multidrug Resistant Cell Line

Contact Info

Product

Resources

About