Evaluation of Methylation at Promoter Regions of Long Non-coding RNAs in Patients with Acute Lymphoblastic Leukemia

Introduction Acute lymphoblastic leukemia (ALL) is a fetal hematologic disorder that is mostly observed in children. Both B and T lymphocytes have been reported to play a role in ALL etiology. Long non-coding RNAs (lncRNAs) are large regulatory molecules with more than 200 nucleotides that participate in various cellular processes. Methylation at the promoter regions of these regulatory molecules has been reported to vary between ALL patients and healthy controls. This study aimed to evaluate methylation status at promoter regions of lncRNAs between these two groups. Methods In the current study, 80 ALL patients and 80 healthy controls were enrolled. The intravenous blood samples were obtained from all patients and controls. The extracted DNA from blood samples underwent sodium bisulfite treatment. Thereafter, methylation levels in the promoter regions of lncRNAs RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were evaluated using methylation specific‑high resolution melting (MS‑HRM). Moreover, the receiver operating characteristic curve (ROC) analysis was performed to examine the sensitivity and specificity of the tests. Results The methylation levels of all studied lncRNAs including RP11-137H2.4 (P =0.001837), RP11-624c23.1 (P = 0.000003), RP11-203E8 (P = 0.000092), RP11-446E9 (P = 0.02447), and RP11-68118.10 (P =0.000086) were significantly increased. ROC curve analysis also showed that all lncRNAs could be used as diagnostic markers. Conclusion This study showed that methylation alterations of lncRNAs could be considered as novel biomarkers for early detection of ALL. Furthermore, owing to the possible role of studied lncRNAs as tumor suppressors, they could be reliable treatment targets for methylation modifications. Further research is still required to elucidate the role of these lncRNAs in ALL etiology.

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LINC00511 exacerbated T-cell acute lymphoblastic leukemia via miR-195-5p/LRRK1 axis

Bioscience Reports ◽

10.1042/bsr20193631 ◽

2020 ◽

Vol 40 (5) ◽

Author(s):

Shengli Li ◽

Wenwen Guo ◽

Huayun Geng ◽

Chao Wang ◽

Shuige Yang ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Lymphoblastic Leukemia ◽

Mediated Effects ◽

Proliferation And Apoptosis ◽

Cell Acute Lymphoblastic Leukemia ◽

Series Of Experiments ◽

Non Coding Rnas

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a malignant disease arising from the abnormal proliferation of T lymphocyte in marrow. Long non-coding RNAs (lncRNAs) are one kind of non-coding RNAs (ncRNAs), which were reported to modulate the initiation or progression of diverse cancers. However, the role of LINC00511 in T-ALL was unknown. To figure out the function and mechanism of LINC00511 in T-ALL, a series of experiments were carried out. Based on the experimental results, we discovered that LINC00511 boosted cell proliferation and invasion, but hindered cell apoptosis in T-ALL cells. Besides, based on bio-informatics tool, miR-195-5p was selected for further exploration. Then, miR-195-5p was validated to bind with LINC00511. Hereafter, LRRK1 was testified to serve as a target gene of miR-195-5p. At last, rescue assays suggested that LRRK1 overexpression restored sh-LINC00511#1-mediated effects on cell proliferation and apoptosis. All in all, LINC00511 exacerbated T-ALL progression via miR-195-5p/LRRK1 axis, implying a potential therapeutic clue for the patients with T-ALL.

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LINC00221 suppresses the malignancy of children acute lymphoblastic leukemia

Bioscience Reports ◽

10.1042/bsr20194070 ◽

2020 ◽

Vol 40 (5) ◽

Author(s):

Man Huang ◽

Jiajia Zheng ◽

Yongya Ren ◽

Jingjing Zhu ◽

Linbing Kou ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Genetic Alterations ◽

Ki 67 ◽

Protein Coding ◽

Proliferation And Apoptosis ◽

Rna Immunoprecipitation ◽

Non Coding Rnas

Abstract As the most common malignant disease in childhood, children acute lymphoblastic leukemia (ALL) is a heterogeneous disease caused by the accumulated genetic alterations. Long non-coding RNAs (lncRNAs) are reported as critical regulators in diseases. GEPIA database indicated that long intergenic non-protein coding RNA 221 (LINC00221) was conspicuously down-regulated in acute myeloid leukemia. However, its expression pattern in ALL has not been revealed. This work was carried out to study the role of LINC00221 in ALL cells. Quantitative real-time PCR (qRT-PCR) quantified LINC00221 expression in ALL cells. The function of LINC00221 in ALL was determined by ki-67 immunofluorescence staining, EdU, TUNEL, JC-1, and caspase-3/8/9 activity assays. RNA pull down and Ago2-RNA immunoprecipitation (RIP) assays investigated the interaction between miR-152-3p and LINC00221 or ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2). Our study revealed the low expression of LINC00221 in ALL cells. Subsequently, LINC00221 was verified to bind with miR-152-3p. Moreover, functional assays pointed out that LINC00221 overexpression posed anti-proliferation and pro-apoptosis effects in ALL cells, and these effects could be separately reversed by miR-152-3p up-regulation. Afterward, LINC00221 was revealed to regulate ATP2A2 expression via sponging miR-152-3p. Additionally, ATP2A2 was verified to involve in regulating LINC00221-mediated ALL cell proliferation and apoptosis. In conclusion, LINC00221 suppressed ALL cell proliferation and boosted ALL cell apoptosis via sponging miR-152-3p to up-regulate ATP2A2.

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The Role of Allogeneic Hematopoietic Stem Cell Transplantation in the Therapy of Patients with Acute Lymphoblastic Leukemia

Current Hematologic Malignancy Reports ◽

10.1007/s11899-012-0116-3 ◽

2012 ◽

Vol 7 (2) ◽

pp. 144-152 ◽

Cited By ~ 9

Author(s):

Partow Kebriaei ◽

L. M. Poon

Keyword(s):

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Lymphoblastic Leukemia ◽

Hematopoietic Stem

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Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

Scientific Reports ◽

10.1038/s41598-021-94469-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Asmaa M. Zahran ◽

Azza Shibl ◽

Amal Rayan ◽

Mohamed Alaa Eldeen Hassan Mohamed ◽

Amira M. M. Osman ◽

...

Keyword(s):

T Cells ◽

Acute Lymphoblastic Leukemia ◽

B Cell ◽

Lymphoblastic Leukemia ◽

Critical Role ◽

Suppressor Cells ◽

Healthy Controls ◽

Blast Cells ◽

Cell Acute Lymphoblastic Leukemia ◽

The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

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The role of miRNA-196a2 genotypes in the susceptibility of acute lymphoblastic leukemia in Egyptian children

Gene Reports ◽

10.1016/j.genrep.2021.101237 ◽

2021 ◽

pp. 101237

Author(s):

N.A. Abdulhafeez ◽

D.M. Abd El Hassib ◽

O.M. Atef ◽

S.G. Ameen

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Egyptian Children

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Inhibition of Autophagy Enhances the Antitumor Effect of Thioridazine in Acute Lymphoblastic Leukemia Cells

Life ◽

10.3390/life11040365 ◽

2021 ◽

Vol 11 (4) ◽

pp. 365

Author(s):

Carina Colturato-Kido ◽

Rayssa M. Lopes ◽

Hyllana C. D. Medeiros ◽

Claudia A. Costa ◽

Laura F. L. Prado-Souza ◽

...

Keyword(s):

Cell Death ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Clinical Problem ◽

Jurkat Cells ◽

Leukemia Cells ◽

Peripheral Mononuclear Blood ◽

Induced Apoptosis ◽

Cure Rates

Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells that affects children and adults. Despite the high cure rates, drug resistance still remains a significant clinical problem, which stimulates the development of new therapeutic strategies and drugs to improve the disease outcome. Antipsychotic phenothiazines have emerged as potential candidates to be repositioned as antitumor drugs. It was previously shown that the anti-histaminic phenothiazine derivative promethazine induced autophagy-associated cell death in chronic myeloid leukemia cells, although autophagy can act as a “double-edged sword” contributing to cell survival or cell death. Here we evaluated the role of autophagy in thioridazine (TR)-induced cell death in the human ALL model. TR induced apoptosis in ALL Jurkat cells and it was not cytotoxic to normal peripheral mononuclear blood cells. TR promoted the activation of caspase-8 and -3, which was associated with increased NOXA/MCL-1 ratio and autophagy triggering. AMPK/PI3K/AKT/mTOR and MAPK/ERK pathways are involved in TR-induced cell death. The inhibition of the autophagic process enhanced the cytotoxicity of TR in Jurkat cells, highlighting autophagy as a targetable process for drug development purposes in ALL.

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