Importância da detecção das mutações no gene FLT3 e no gene NPM1 na leucemia mieloide aguda - Classificação da Organização Mundial de Saúde 2008

Licínio, Marley Aparecida; Silva, Maria Cláudia Santos da

doi:10.1590/s1516-84842010000600012

Cited by 4 publications

(3 citation statements)

References 52 publications

(78 reference statements)

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“…The first mutation is internal tandem duplication (ITD) in juxtamembrane (JM) domain and a point mutation in tyrosine kinase domain. FLT3-ITD gene mutation has been known as a strong prognostic factor in AML patients and it is related to disease progression, high relapse rate and low overall survival for 10 months (4,12,13). The frequency of FLT3-ITD gene mutation in AML is 21-24%.…”

Section: Discussionmentioning

confidence: 99%

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

et al. 2020

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Scan to discover online Background & Objective: FLT3-ITD has been recently used as a molecular prognostic marker for risk classification in acute myeloid leukemia (AML) therapy. In this study we aimed to investigate the association of FLT3-ITD gene mutation with bone marrow blast cell count, CD34 expression as malignant cell burden, cyclin D1 and Bcl-xL expressions as indexes of cell proliferation and anti-apoptosis and human equilibrative nucleoside transporter 1 (hENT1) expression as cytarabine transporter during AML treatment. Methods: We investigated FLT3-ITD mutations, bone marrow blast cell count, CD34, cyclin D1, Bcl-xL and hENT1 expression in bone marrow aspirates from 22 de novo AML patients in a cross sectional study. Results: FLT3-ITD mutations were observed in 5 out of 22 de novo AML patients (22.7%). Patient with FLT3-ITD mutations had higher blast cell counts (79.5% vs 56.1%, P=0.004). In patients with FLT3-ITD mutations, CD34 and cyclin D1 expressions were higher (MFI 328.80 vs 25.78, P=0.003 and MFI 74.51 vs 57.15 P=0.005) than the patients without mutations. hENT1 expression in AML with FLT3-ITD mutation was lower (MFI 29.64 versus 56.32, P=0.0000) than in mutation-free AML. There was no significant difference in Bcl-xL expression between patients with and without mutations (P=0.61). Conclusion: A significant association was found between FLT3-ITD gene mutations in AML patients with bone marrow blast cell count, CD34, cyclin D1 and hENT1 expressions, however no association was obtained with Bcl-xL expression. These findings support the role of such mutation in pathogenesis of AMLand its contribution in rearrangement of standard therapy with cytarabine in management of AML.

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Section: Discussionmentioning

confidence: 99%

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

et al. 2020

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“…The dimerization makes the juxta-membrane region lose its auto-inhibitory capability and permits dimerization of the receptors independent of the ligand, leading to auto-phosphorylation and autonomous growth of mutant cells (Kiyoi et al, 1998). In the case of ITD, auto-phosphorylation of the FLT3 receptor occurs, leading to its permanent activation, which eventually results in the stimulation of cell signaling pathways such as ERK and STAT (Griffith et al, 2004;Licínio & Silva, 2010).…”

Section: Npm1 and Flt3-itd Mutations In Amlmentioning

confidence: 99%

The potential role of nucleophosmin (NPM1) in the development of cancer

Dermani

Khoei

Afshar

et al. 2021

Journal Cellular Physiology

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Nucleophosmin (NPM1) is a well-known nucleocytoplasmic shuttling protein that performs several cellular functions such as ribosome biogenesis, chromatin remodeling, genomic stability, cell cycle progression, and apoptosis. NPM1 has been identified to be necessary for normal cellular functions, and its altered regulation by overexpression, mutation, translocation, loss of function, or sporadic deletion can lead to cancer and tumorigenesis. In this review, we focus on the gene and protein structure of NPM1 and its physiological roles. Finally, we discuss the association of NPM1 with various types of cancer including solid tumors and leukemia.

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“…A Leucemia Linfoide Aguda (LLA) é uma patologia de origem genética que ocorre pela proliferação descontrolada de células de origem linfoide B ou T imaturas, ou seja, blastos, principalmente na medula óssea, mas também podendo acometer outros tecidos linfoides (Licínio;Silva, 2010;Rocha, 2012).…”

Section: Leucemia Linfoide Agudaunclassified

Imunoterapia dirigida com células T-CAR para tratamento de leucemia linfoide aguda

Souza

Silva

Miranda³

et al. 2020

RSD

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Introdução: A imunoterapia com células T-CAR tem sido utilizada como um método alternativo de tratamento da Leucemia Linfóide Aguda (LLA). A LLA é uma patologia na qual há o aumento exacerbado de células jovens imaturas, visto que seus precursores celulares mais afetados são as células T e, na maioria das vezes, células B. O objetivo deste artigo foi explanar sobre a técnica de imunoterapia com células T-CAR, assim como o seu funcionamento. Metodologia: Trata-se de uma revisão bibliográfica de abordagem qualitativa do tipo exploratória, dos quais, foram realizadas buscas nas principais bases eletrônicas nacionais e internacionais: Pubmed, Eletronic Library On-line (SCIELO) Biblioteca virtual de saúde (Bvs), Cell, Science, Nature e Scholar Google no período de 2007 a 2018. Resultados: A LLA é uma patologia que acomete a produção de células sanguíneas como eritrócitos, megacariócitos e granulócitos, isso se deve devido à propagação elevada de blastos na medula óssea. Esta doença tem como tratamento convencional principalmente a quimioterapia e a radioterapia, como também o transplante de células tronco, entretanto esses métodos podem vir a causar diversas complicações ao paciente. A terapia com células T-CAR tem como alvo a destruição de células B do indivíduo, através do reconhecimento de antígenos específicos dessas células (CD19). Conclusão: O tratamento com as células T-CAR demonstra efeitos adversos de baixa gravidade comparado às terapias convencionais (quimioterapia e radioterapia). Portanto, essa imunoterapia pode favorecer no futuro um elevado número de pacientes no combate não apenas a LLA, mas também a diversas outras doenças.

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Importância da detecção das mutações no gene FLT3 e no gene NPM1 na leucemia mieloide aguda - Classificação da Organização Mundial de Saúde 2008

Cited by 4 publications

References 52 publications

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

The potential role of nucleophosmin (NPM1) in the development of cancer

Imunoterapia dirigida com células T-CAR para tratamento de leucemia linfoide aguda

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