The <i>P2X7</i> Receptor Gene A1513C Polymorphism Does Not Contribute to Risk of Familial or Sporadic Chronic Lymphocytic Leukemia

Sellick, Gabrielle S.; Rudd, Matthew; Eve, Paul D.; Allinson, Ruth; Matutes, Estella; Catovsky, Daniel; Houlston, Richard S.

doi:10.1158/1055-9965.1065.13.6

Cited by 22 publications

(1 citation statement)

References 10 publications

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“…Outro estudo mostrou que este polimorfismo estava correlacionado com a melhora nos resultados clínicos na B-LLC, aumentando a sobrevida dos pacientes (Thunberg et al, 2002). Nos anos seguintes, os estudos correlacionaram pacientes saudáveis e pacientes com B-LLC familiar e/ou esporádica, e a relação do polimorfismo 1513 A->C com essa doença foi invalidada em todos os aspectos estudados anteriormente: patogênese, progressão, diagnóstico e sobrevida (Starczynski et al, 2003;Zhang et al, 2003;Nückel et al, 2004;Sellick et al, 2004).…”

Section: Receptores Purinérgicos E Leucemiaunclassified

Regulação purinérgica do sistema hematopoético

Souza¹,

Costa²,

Paredes-Gamero³

et al. 2021

Sinalização Purinérgica: Implicações Fisiopatológicas

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A regulação da quiescência, autorenovação, proliferação, diferenciação, e morte da célula-tronco hematopoética (CTH) é o âmago deste sistema. Este processo, conhecido como hematopoese, é regulado por diversos sinalizadores humorais, principalmente por moléculas conhecidas como citocinas. Entretanto, ademais das citocinas, outros sinalizadores, como o ATP, também são relevantes neste processo. O ATP é um sinalizador importante em diversos sistemas, mas intriga a forma de regulação do sistema hematopoético, porque os receptores de ATP -P2 são expressos desde as células mais primitivas hematopoéticas, até os diferentes tipos de células maduras deste sistema. Além dos receptores P2, enzimas que degradam o ATP em metabólitos como ADP e adenosina fazem parte desta regulação formando um complexo esquema de regulação purinérgica (Figura 1).Embora o papel mais marcante e investigado dos receptores P2 seja em processos de regulação do sistema imune, recentes trabalhos vêm mostrando o papel fundamental da regulação purinérgica no desenvolvimento hematopoético e as consequências biológicas das alterações na expressão e função dos receptores e enzimas que regulam o sistema purinérgico. Neste capítulo, descreveremos as

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Section: Receptores Purinérgicos E Leucemiaunclassified

Regulação purinérgica do sistema hematopoético

Souza¹,

Costa²,

Paredes-Gamero³

et al. 2021

Sinalização Purinérgica: Implicações Fisiopatológicas

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P2X7 receptor: Death or life?

Adinolfi

Pizzirani

Idzko

et al. 2005

Purinergic Signalling

121

123

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The P2X 7 plasma membrane receptor is an intriguing molecule that is endowed with the ability to kill cells, as well as to activate many responses and even stimulate proliferation. Here, the authors give an overview on the multiplicity and complexity of P2X 7 -mediated responses, discussing recent information on this receptor. Particular attention has been paid to early and late signs of apoptosis and necrosis linked to activation of the receptor and to the emerging field of P2X 7 function in carcinogenesis.P2X 7 : From an elusive receptor to an ATP-gated channel/pore The P2X 7 receptor (P2X 7 R) for extracellular ATP is expressed by a variety of cell types as different as neurons, macrophages, dendritic and microglial cells, fibroblasts, lymphocytes, and endothelial cells. At least a subpopulation of human osteoblasts also express P2X 7 [1]. Expression of the receptor has been demonstrated in human fibroblasts [2,3] and epithelia from the human bladder [4,5], human and rat uterus [6,7], male genital organs of the rats [8], human fetal keratinocytes [9] and mouse parotid acinar and duct cells [10].Although interest in this molecule has increased exponentially since the late 1990s, initial observations on its peculiar biochemical properties go back to the 1970s, when Cockcroft and Gomperts reported that extracellular ATP caused degranulation and striking morphological changes in rat mast cells [11]. These authors also hypothesized that cell responses triggered by ATP, such as histamine secretion and phosphatidyl inositol formation, were due to activation of an as yet unknown receptor (the FATP receptor_) activated by the fully dissociated ATP form (ATP 4j ) [12]. Based on its intriguing ability to cause a reversible permeabilization of the plasma membrane, this receptor was also referred to as the Fpermeabilizing ATP receptor_ later named P2Z [13]. P2Z was described not only in rat mast cells but also in mouse macrophages [14,15]. Following these early observations, the peculiar pharmacological and biochemical properties of the P2Z receptor were recognized in many other cells such as human macrophages, human B lymphocytes, mouse microglial cells, mouse and human monocyte-derived dendritic cells.The permeabilizing ATP receptor was cloned in 1996 from a rat brain library and named P2X 7 for its homology with the other P2X receptors [16]. P2X 7 is a 595 AA protein with a predicted structure comprising two transmembrane domains and a bulky extracellular cysteine rich region, with conserved lysine and glycine residues and several potential N-linked glycosylation sites, followed by a long stretch (from Phe 188 to Val 321 ) forming six putative antiparallel b sheets. The amino and carboxyl-terminal domains are both cytoplasmic. Similarities have been found between the b sheets region and the catalytic domains of class II aminoacylYtRNA synthetases [17]. These b sheets are likely to include residues comprising the ATP-binding site, since substitution of two aminoacids comprised in this region, Lys 193 and Lys 311...

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Involvement of P2 receptors in hematopoiesis and hematopoietic disorders, and as pharmacological targets

Filippin

Souza

Júnior

et al. 2019

Purinergic Signalling

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Several reports have shown the presence of P2 receptors in hematopoietic stem cells (HSCs). These receptors are activated by extracellular nucleotides released from different sources. In the hematopoietic niche, the release of purines and pyrimidines in the milieu by lytic and nonlytic mechanisms has been described. The expression of P2 receptors from HSCs until maturity is still intriguing scientists. Several reports have shown the participation of P2 receptors in events associated with modulation of the immune system, but their participation in other physiological processes is under investigation. The presence of P2 receptors in HSCs and their ability to modulate this population have awakened interest in exploring the involvement of P2 receptors in hematopoiesis and their participation in hematopoietic disorders. Among the P2 receptors, the receptor P2X7 is of particular interest, because of its different roles in hematopoietic cells (e.g., infection, inflammation, cell death and survival, leukemias and lymphomas), making the P2X7 receptor a promising pharmacological target. Additionally, the role of P2Y12 receptor in platelet activation has been well-documented and is the main example of the importance of the pharmacological modulation of P2 receptor activity. In this review, we focus on the role of P2 receptors in the hematopoietic system, addressing these receptors as potential pharmacological targets.

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The P2X7 Receptor Gene A1513C Polymorphism Does Not Contribute to Risk of Familial or Sporadic Chronic Lymphocytic Leukemia

Cited by 22 publications

References 10 publications

Regulação purinérgica do sistema hematopoético

Regulação purinérgica do sistema hematopoético

P2X7 receptor: Death or life?

Involvement of P2 receptors in hematopoiesis and hematopoietic disorders, and as pharmacological targets

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