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1.
Sheng Wu Gong Cheng Xue Bao ; 37(11): 3933-3944, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34841796

RESUMO

Long noncoding RNAs (lncRNAs) are a class of RNA molecules that are greater than 200 nt in length and do not have protein-coding capabilities or encode micropeptides only. LncRNAs are involved in the regulation of cell proliferation, differentiation, apoptosis and other biological processes, and are closely associated with the occurrence, recurrence and metastasis of a variety of malignant hematologic diseases. This article summarizes the function, regulatory mechanism and potential clinical application of lncRNAs in leukemia. In general, lncRNAs regulate the occurrence and development of leukemia and the multi-drug resistance in chemotherapy through epigenetic modification, ribosomal RNA transcription, competitive binding with miRNA, modulating glucose metabolic pathway, and activating tumor-related signaling pathway. Studies on lncRNAs provide new references for understanding the pathogenesis of leukemia, uncovering new prognostic markers and potential therapeutic targets, and addressing the problems of drug resistance and post-treatment recurrence in patients in clinical treatment of leukemia.


Assuntos
Leucemia , MicroRNAs , Neoplasias , RNA Longo não Codificante , Proliferação de Células , Humanos , Leucemia/genética , RNA Longo não Codificante/genética
2.
J Med Case Rep ; 15(1): 567, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823580

RESUMO

BACKGROUND: Escherichia coli has appeared as an important opportunistic pathogen responsible for nosocomial infections in patients with immunodeficiency, particularly in leukemia patients. New Delhi metallo-beta-lactamase is an enzyme originally found in Enterobacteriaceae. CASE PRESENTATION: In this study, 80 isolates of Escherichia coli and Klebsiella pneumoniae were collected over the course of 2 years from two medical centers in Tehran, Iran. Production of carbapenemase was detected in the isolates using modified Hodge test. New Delhi metallo-beta-lactamase-1 genes were detected by polymerase chain reaction amplification with specific primers. Two New Delhi metallo-beta-lactamase-1-producing Escherichia coli strains were isolated from two Iranian patients with leukemia. These two patients were 6 and 15 years old, one female and the other male, from two oncology centers in Iran. The isolates were resistant to carbapenems (imipenem, meropenem), and two isolates were positive for carbapenemase production by modified Hodge test. CONCLUSIONS: The emergence of New Delhi metallo-beta-lactamase-1-producing Escherichia coli is a threat for leukemia patients in oncology and hematology departments. We conclude that the incidence of multidrug resistant pathogens has increased among patients with leukemia and is life threatening.


Assuntos
Escherichia coli , Leucemia , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , beta-Lactamases/genética
3.
BMC Bioinformatics ; 22(Suppl 5): 94, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749635

RESUMO

BACKGROUND: Differentiating and counting various types of white blood cells (WBC) in bone marrow smears allows the detection of infection, anemia, and leukemia or analysis of a process of treatment. However, manually locating, identifying, and counting the different classes of WBC is time-consuming and fatiguing. Classification and counting accuracy depends on the capability and experience of operators. RESULTS: This paper uses a deep learning method to count cells in color bone marrow microscopic images automatically. The proposed method uses a Faster RCNN and a Feature Pyramid Network to construct a system that deals with various illumination levels and accounts for color components' stability. The dataset of The Second Affiliated Hospital of Zhejiang University is used to train and test. CONCLUSIONS: The experiments test the effectiveness of the proposed white blood cell classification system using a total of 609 white blood cell images with a resolution of 2560 × 1920. The highest overall correct recognition rate could reach 98.8% accuracy. The experimental results show that the proposed system is comparable to some state-of-art systems. A user interface allows pathologists to operate the system easily.


Assuntos
Aprendizado Profundo , Leucemia , Medula Óssea , Humanos , Processamento de Imagem Assistida por Computador , Leucócitos
5.
Blood Adv ; 5(22): 4535-4548, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34614508

RESUMO

Aside from cell intrinsic factors such as genetic alterations, immune dysregulation in the bone marrow (BM) microenvironment plays a role in the development and progression of myelodysplastic syndromes (MDS). However, the prognostic implications of various immune cells in patients with MDS remain unclear. We adopted CIBERSORTx to estimate the relative fractions of 22 subtypes of immune cells in the BM of 316 patients with MDS and correlated the results with clinical outcomes. A lower fraction of unpolarized M0 macrophages and higher fractions of M2 macrophages and eosinophils were significantly associated with inferior survival. An immune cell scoring system (ICSS) was constructed based on the proportion of these 3 immune cells in the BM. The ICSS high-risk patients had higher BM blast counts, higher frequencies of poor-risk cytogenetics, and more NPM1, TP53, and WT1 mutations than intermediate- and low-risk patients. The ICSS could stratify patients with MDS into 3 risk groups with distinct leukemia-free survival and overall survival among the total cohort and in the subgroups of patients with lower and higher disease risk based on the revised International Prognostic Scoring System (IPSS-R). The prognostic significance of ICSS was also validated in another independent cohort. Multivariable analysis revealed that ICSS independently predicted prognosis, regardless of age, IPSS-R, and mutation status. Bioinformatic analysis demonstrated a significant correlation between high-risk ICSS and nuclear factor κB signaling, oxidative stress, and leukemic stem cell signature pathways. Further studies investigating the mechanistic insight into the crosstalk between stem cells and immune cells are warranted.


Assuntos
Leucemia , Síndromes Mielodisplásicas , Medula Óssea , Análise Citogenética , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Prognóstico , Microambiente Tumoral
6.
Adv Exp Med Biol ; 1329: 181-203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34664240

RESUMO

The bone marrow (BM) is a complex organ located within the cavities of bones. The main function of the BM is to produce all the blood cells required for a normal healthy blood system. As with any major organ, many diseases can arise from errors in bone marrow function, including non-malignant disorders such as anaemia and malignant disorders such as leukaemias. This article will explore the role of the bone marrow, in normal and diseased haematopoiesis, with an emphasis on the requirement for intercellular mitochondrial transfer in leukaemia.


Assuntos
Neoplasias Hematológicas , Leucemia , Medula Óssea/metabolismo , Neoplasias Hematológicas/metabolismo , Humanos , Leucemia/metabolismo , Mitocôndrias , Microambiente Tumoral
7.
Anticancer Res ; 41(10): 4929-4936, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593440

RESUMO

BACKGROUND/AIM: A new set of LQB-nitrones and analogues was synthesized to evaluate anticancer activity based on the substitution of the terpenyl moiety of the antileukemic compound LQB-278 by the conformationally restricted cinnamyl ether. MATERIALS AND METHODS: A structure-activity relationship study was performed in vitro on Jurkat cells to screen the antileukemic activity of LQB-nitrones and analogues and elucidate the mechanisms of action of the most active derivatives. RESULTS: The cynamyl ramification and its ortho position aldehyde substitution improved the antileukemic activity. Three compounds showed an in vitro antiproliferative action, but only 5b induced apoptosis. Analysis of the molecular mechanisms showed increased expression of the cell cycle inhibitor p21CIP1/WAF1/Sdi1, caspase 3, Fas receptor, and Bax/Bcl-2 ratio. CONCLUSION: The cinnamyl derivative 5b (LQB-461) presented higher antileukemic effects than the prototype terpenyl nitrone, inducing Jurkat cell death by activating both extrinsic and intrinsic pathways of apoptosis. Therefore, this compound is a new promising candidate drug against leukemia.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Leucemia/tratamento farmacológico , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/farmacologia , Apoptose , Proliferação de Células , Humanos , Leucemia/patologia , Células Tumorais Cultivadas
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1387-1393, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627415

RESUMO

OBJECTIVE: To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562. METHODS: CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC50 were calculated. The effects of ZL-n-91 to the cycle of L1210 and K562 cells was detected by PE single staining, and the effects of ZL-n-91 to the apoptosis of L1210 and K562 cells was detected by PE/7AA-D double staining. Western blot was used to detect the effect of ZL-n-91 to the expression levels of apoptosis related proteins. Subcutaneous tumor transplantation model of acute lymphoblastic leukemia L1210 was established in the nude mice, and the inhibitory effect of oral administration of ZL-n-91 to the xenograft was observed. RESULTS: ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05). CONCLUSION: The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.


Assuntos
Leucemia , Inibidores da Fosfodiesterase 4 , Animais , Proliferação de Células , Humanos , Células K562 , Camundongos , Camundongos Nus , Inibidores da Fosfodiesterase 4/farmacologia
10.
MMW Fortschr Med ; 163(19): 28, 2021 11.
Artigo em Alemão | MEDLINE | ID: mdl-34708363
11.
Nat Commun ; 12(1): 5773, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599159

RESUMO

Protein localisation and translocation between intracellular compartments underlie almost all physiological processes. The hyperLOPIT proteomics platform combines mass spectrometry with state-of-the-art machine learning to map the subcellular location of thousands of proteins simultaneously. We combine global proteome analysis with hyperLOPIT in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during a lipopolysaccharide (LPS)-induced inflammatory response. We report a highly dynamic proteome in terms of both protein abundance and subcellular localisation, with alterations in the interferon response, endo-lysosomal system, plasma membrane reorganisation and cell migration. Proteins not previously associated with an LPS response were found to relocalise upon stimulation, the functional consequences of which are still unclear. By quantifying proteome-wide uncertainty through Bayesian modelling, a necessary role for protein relocalisation and the importance of taking a holistic overview of the LPS-driven immune response has been revealed. The data are showcased as an interactive application freely available for the scientific community.


Assuntos
Inflamação/metabolismo , Leucemia/metabolismo , Leucemia/patologia , Lipopolissacarídeos/farmacologia , Proteômica , Algoritmos , Anti-Infecciosos/metabolismo , Anti-Inflamatórios/metabolismo , Apresentação do Antígeno , Autofagossomos/metabolismo , Teorema de Bayes , Pontos de Checagem do Ciclo Celular , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Forma Celular , Humanos , Imunidade , Inflamação/patologia , Leucemia/imunologia , Ativação Linfocitária/imunologia , Lisossomos/metabolismo , Proteínas de Neoplasias/metabolismo , Transporte Proteico , Proteoma/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Células THP-1 , Fatores de Tempo , Vesículas Transportadoras/metabolismo , Regulação para Cima , Proteínas rho de Ligação ao GTP/metabolismo
12.
In Vivo ; 35(6): 3253-3260, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34697156

RESUMO

BACKGROUND/AIM: Demethoxycurcumin (DMC), one of the components of curcuminoids, has antitumor activities in many human cancer cells and is known to induce apoptosis in human leukemia cells. However, there are no reports showing the effects of DMC on the immune response in leukemia mice in vivo. Herein, we evaluated the impact of DMC on immune responses in WEHI-3-generated leukemia mice in vivo. MATERIALS AND METHODS: Fifty male BALB/c mice were separated randomly into five groups. Group I is normal mice, and groups II-V mice of generated leukemia by WEHI-3 cells. Group II-V mice were intraperitoneally injected with dimethyl sulfoxide (DMSO, as the positive control), 15, 30, and 60 mg/kg of DMC, respectively, every two days for 14 days. The body weight, blood, peritoneal fluid, liver, and spleen were individually analyzed. RESULTS: DMC did not significantly affect animal appearance and body weight. It decreased liver and spleen weight at a high dose. DMC did not affect the cluster of differentiation 3 (CD3) and CD19 cell populations but induced decrease of CD11b at 30 mg/kg treatment. However, DMC at low dose significantly increased the cluster of macrophage (Mac-3) cell populations, but at high dose it decreased them. DMC increased macrophage phagocytosis from peripheral blood mononuclear cells at 15 mg/kg treatment and peritoneal cavity at 15, 30 and 60 mg/kg of DMC treatments. DMC did not significantly affect the cytotoxic activity of natural killer (NK) cells. Furthermore, DMC decreased B and T cell proliferation at high doses. CONCLUSION: DMC elevated macrophage phagocytosis in leukemia mice in vivo.


Assuntos
Leucemia , Leucócitos Mononucleares , Animais , Linhagem Celular Tumoral , Diarileptanoides , Leucemia/tratamento farmacológico , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose
13.
Gen Physiol Biophys ; 40(5): 397-407, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34602453

RESUMO

The present study was conducted to explore the anti-acute myeloid leukaemia (AML) effects of leonurine. HL-60 and U-937 cells were used to assess the antileukaemia effect of leonurine in vitro, and HL-60 and U-937 xenograft nude mice were used to evaluate its antitumour effect in vivo. Leonurine inhibited the proliferation of HL-60 and U-937 cells in a time- and dose-dependent manner. Moreover, leonurine therapy prevented the growth of tumours in both xenograft animal models. Leonurine could induce apoptosis in HL-60 and U-937 cells. The cytotoxic effects of leonurine on HL-60 and U-937 cells were associated with an increased ratio of Bax/Bcl-2, activation of caspase-3, caspase-8 and caspase-9, and increased expression of cytochrome c in the cytoplasm. Leonurine inhibited activation of the PI3K/Akt pathway in HL-60 and U-937 cells by lowering the phosphorylation levels of PI3K and Akt. Our results indicate that leonurine is a potential anti-AML agent, and this activity may be associated with its repression of the phosphorylation of PI3K and Akt.


Assuntos
Leucemia , Fosfatidilinositol 3-Quinases , Animais , Ácido Gálico/análogos & derivados , Células HL-60 , Humanos , Camundongos , Camundongos Nus
14.
Orv Hetil ; 162(43): 1744-1748, 2021 10 24.
Artigo em Húngaro | MEDLINE | ID: mdl-34689135

RESUMO

Összefoglaló. Az emlotumor miatt kezelt, majd gondozott beteget - több tünetmentes év után - fejfájás, szédülés, ataxia, megváltozott, furcsa viselkedés, emlékezetzavar és dezorientáció miatt neurológiai, majd belgyógyászati osztályokon vizsgálták. Az alapos kivizsgálás ellenére a tüneteit magyarázó organikus eltérést nem igazoltak, ugyanakkor már a kezdetektol felmerült a szomatizációs tünetképzés lehetosége, ezért pszichiátriai osztályos felvételére került sor. Az elvégzett vizsgálatok, illetve a klinikai kép regresszív állapotot valószínusítettek. Terápiás próbálkozásaink ellenére a páciens állapota romlott, végül a megismételt neurológiai vizsgálatok meningitis carcinomatosát igazoltak. Az esettel szemléltetni kívánjuk, hogy a beteg premorbid muködési nívója, személyiségstruktúrája hogyan képes befolyásolni az ellátószemélyzetet, milyen külso és belso konfliktusokat válthat ki. A diagnózishoz vezeto folyamat bemutatásával fel kívánjuk hívni a figyelmet az interdiszciplináris együttmuködés fontosságára. Orv Hetil. 2021; 162(43): 1744-1748. Summary. Our patient with known breast cancer in her past medical history was hospitalized - after several asymptomatic years - for headache, dizziness, ataxia, changed behaviour and disorientation. Thorough internal and neurologic investigations did not find any disease underlying her symptoms, therefore the possibility of somatization disorder was raised. Despite lege artis therapeutic interventions carried out on the psychiatry ward, the patient's condition deteriorated and repeated neurological examinations eventually revealed carcinomatous meningitis. With this case, we would like to illustrate how the patient's premorbid function level and personality features might influence the attitude and opinion of the health care personnel, and what kind of external and internal conflicts might be triggered. By presenting the complexity of the diagnostic work-up, we would like to emphasize the importance of interdisciplinary cooperation in the interest of our patients. Orv Hetil. 2021; 162(43): 1744-1748.


Assuntos
Leucemia , Carcinomatose Meníngea , Feminino , Humanos , Vertigem
16.
Int J Nanomedicine ; 16: 6205-6216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526768

RESUMO

Introduction: Traditional cancer therapies may have incomplete eradication of cancer or destroy the normal cells. Nanotechnology solves the demerit by a guide in surgical resection of tumors, targeted chemotherapies, selective to cancerous cells, etc. This new technology can reduce the risk to the patient and automatically increased the probability of survival. Toward this goal, novel iron oxide nanoparticles (IONPs) coupled with leukemia anti-cancer drug were prepared and assessed. Methods: The IONPs were prepared by the co-precipitation method using Fe+3/Fe+2ratio of 2:1. These IONPs were used as a carrier for chlorambucil (Chloramb), where the IONPs serve as the cores and chitosan (CS) as a polymeric shell to form Chloramb-CS-IONPs. The products were characterized using transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) analysis, Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM) analyses, and thermal gravimetric analysis (TGA). Results: The as-prepared IONPs were found to be magnetite (Fe3O4) and were coated by the CS polymer/Chloramb drug for the formation of the Chloramb-CS-IONPs. The average size for CS-IONPs and Chloramb-CS-IONPs nanocomposite was found to be 15 nm, with a drug loading of 19% for the letter. The release of the drug from the nanocomposite was found to be of a controlled-release manner with around 89.9% of the drug was released within about 5000 min and governed by the pseudo-second order. The in vitro cytotoxicity studies of CS-IONPs and Chloramb-CS-IONPs nanocomposite were tested on the normal fibroblast cell lines (3T3) and leukemia cancer cell lines (WEHI). Chloramb in Chloramb-CS-IONPs nanocomposite was found to be more efficient compared to its free form. Conclusion: This work shows that Chloramb-CS-IONPs nanocomposite is a promising candidate for magnetically targeted drug delivery for leukemia anti-cancer agents.


Assuntos
Quitosana , Leucemia , Nanopartículas de Magnetita , Clorambucila , Sistemas de Liberação de Medicamentos , Humanos , Leucemia/tratamento farmacológico , Nanopartículas Magnéticas de Óxido de Ferro , Espectroscopia de Infravermelho com Transformada de Fourier
17.
J Biol Chem ; 297(4): 101170, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492268

RESUMO

Elevated intracellular levels of dNTPs have been shown to be a biochemical marker of cancer cells. Recently, a series of mutations in the multifunctional dNTP triphosphohydrolase (dNTPase), sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1), have been reported in various cancers. Here, we investigated the structure and functions of SAMHD1 R366C/H mutants, found in colon cancer and leukemia. Unlike many other cancer-specific mutations, the SAMHD1 R366 mutations do not alter cellular protein levels of the enzyme. However, R366C/H mutant proteins exhibit a loss of dNTPase activity, and their X-ray structures demonstrate the absence of dGTP substrate in their active site, likely because of a loss of interaction with the γ-phosphate of the substrate. The R366C/H mutants failed to reduce intracellular dNTP levels and restrict HIV-1 replication, functions of SAMHD1 that are dependent on the ability of the enzyme to hydrolyze dNTPs. However, these mutants retain dNTPase-independent functions, including mediating dsDNA break repair, interacting with CtIP and cyclin A2, and suppressing innate immune responses. Finally, SAMHD1 degradation in human primary-activated/dividing CD4+ T cells further elevates cellular dNTP levels. This study suggests that the loss of SAMHD1 dNTPase activity induced by R366 mutations can mechanistically contribute to the elevated dNTP levels commonly found in cancer cells.


Assuntos
Neoplasias do Colo , Leucemia , Mutação de Sentido Incorreto , Proteínas de Neoplasias , Proteína 1 com Domínio SAM e Domínio HD , Substituição de Aminoácidos , Linhagem Celular , Neoplasias do Colo/enzimologia , Neoplasias do Colo/genética , Ciclina A2/química , Ciclina A2/genética , Ciclina A2/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Endodesoxirribonucleases/química , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Humanos , Leucemia/enzimologia , Leucemia/genética , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteína 1 com Domínio SAM e Domínio HD/química , Proteína 1 com Domínio SAM e Domínio HD/genética , Proteína 1 com Domínio SAM e Domínio HD/metabolismo , Relação Estrutura-Atividade
18.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576214

RESUMO

Endogenous glucocorticoids (GCs) are steroid hormones that signal in virtually all cell types to modulate tissue homeostasis throughout life. Also, synthetic GC derivatives (pharmacological GCs) constitute the first-line treatment in many chronic inflammatory conditions with unquestionable therapeutic benefits despite the associated adverse effects. GC actions are principally mediated through the GC receptor (GR), a ligand-dependent transcription factor. Despite the ubiquitous expression of GR, imbalances in GC signalling affect tissues differently, and with variable degrees of severity through mechanisms that are not completely deciphered. Congenital or acquired GC hypersensitivity or resistance syndromes can impact responsiveness to endogenous or pharmacological GCs, causing disease or inadequate therapeutic outcomes, respectively. Acquired GC resistance is defined as loss of efficacy or desensitization over time, and arises as a consequence of chronic inflammation, affecting around 30% of GC-treated patients. It represents an important limitation in the management of chronic inflammatory diseases and cancer, and can be due to impairment of multiple mechanisms along the GC signalling pathway. Among them, activation of the mitogen-activated protein kinases (MAPKs) and/or alterations in expression of their regulators, the dual-specific phosphatases (DUSPs), have been identified as common mechanisms of GC resistance. While many of the anti-inflammatory actions of GCs rely on GR-mediated inhibition of MAPKs and/or induction of DUSPs, the GC anti-inflammatory capacity is decreased or lost in conditions of excessive MAPK activation, contributing to disease susceptibility in tissue- and disease- specific manners. Here, we discuss potential strategies to modulate GC responsiveness, with the dual goal of overcoming GC resistance and minimizing the onset and severity of unwanted adverse effects while maintaining therapeutic potential.


Assuntos
Regulação da Expressão Gênica , Glucocorticoides/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Animais , Doenças Autoimunes/terapia , Doença Crônica , Ativação Enzimática , Heterozigoto , Humanos , Inflamação/metabolismo , Leucemia/terapia , Erros Inatos do Metabolismo/metabolismo , Camundongos , Mutação , Polimorfismo Genético , Isoformas de Proteínas , Receptores de Glucocorticoides/deficiência , Transtornos Respiratórios/terapia , Transdução de Sinais , Dermatopatias/terapia , Resultado do Tratamento
20.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576226

RESUMO

Genome engineering makes the precise manipulation of DNA sequences possible in a cell. Therefore, it is essential for understanding gene function. Meganucleases were the start of genome engineering, and it continued with the discovery of Zinc finger nucleases (ZFNs), followed by Transcription activator-like effector nucleases (TALENs). They can generate double-strand breaks at a desired target site in the genome, and therefore can be used to knock in mutations or knock out genes in the same way. Years later, genome engineering was transformed by the discovery of clustered regularly interspaced short palindromic repeats (CRISPR). Implementation of CRISPR systems involves recognition guided by RNA and the precise cleaving of DNA molecules. This property proves its utility in epigenetics and genome engineering. CRISPR has been and is being continuously successfully used to model mutations in leukemic cell lines and control gene expression. Furthermore, it is used to identify targets and discover drugs for immune therapies. The descriptive and functional genomics of leukemias is discussed in this study, with an emphasis on genome engineering methods. The CRISPR/Cas9 system's challenges, viewpoints, limits, and solutions are also explored.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Regulação Leucêmica da Expressão Gênica , Leucemia/genética , Animais , Linhagem Celular Tumoral , Ensaios Clínicos como Assunto , Dano ao DNA , Técnicas de Inativação de Genes , Engenharia Genética/métodos , Genoma Humano , Genômica/métodos , Humanos , Sistema Imunitário , Mutação , Segurança do Paciente , RNA/metabolismo , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética
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