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The P2Y 11 receptor is a member of the purinergic receptor family. It has been overlooked, somewhat due to the lack of a P2ry11 gene orthologue in the murine genome, which prevents the generation of knockout mice, which have been so helpful for defining the roles of other P2Y receptors. Furthermore, some of the studies reported to date have methodological shortcomings, making it difficult to determine the function of P2Y 11 with certainty. In this review, we discuss the lack of a murine BP2Y 11 -like receptor^and highlight the limitations of the currently available methods used to investigate the P2Y 11 receptor. These methods include protein recognition with antibodies that show very little specificity, gene expression studies that completely overlook the existence of a fusion transcript between the adjacent PPAN gene and P2RY11, and agonists/antagonists reported to be specific for the P2Y 11 receptor but which have not been tested for activity on numerous other adenosine 5′-triphosphate (ATP)-binding receptors. We suggest a set of criteria for evaluating whether a dataset describes effects mediated by the P2Y 11 receptor. Following these criteria, we conclude that the current evidence suggests a role for P2Y 11 in immune activation with cell typespecific effects.

Precursor B-cell acute lymphoblastic leukemia (B-ALL), a frequent malignancy in children, is characterized by recurrent primary numerical or structural alterations that provide specific molecular markers of the developing malignant clone. 1 The most common alterations, accounting for .50% of all cases, are high hyperdiploidy (51-67 chromosomes) and the chromosomal translocation t(12;21) that generates the ETV6-RUNX1 (synonymous with TEL-AML1) fusion gene. 2 Studies that use monozygotic twins concordant for leukemia, retrospective analyses of archived neonatal blood spots, and molecular screening of umbilical cord blood (UCB) have demonstrated that these subtypes of B-ALL frequently emerge before birth during fetal hematopoiesis. 1,[3][4][5] Both alterations are only mildly oncogenic and require secondary mutations for disease onset. This requirement partially explains the long latency of these leukemias, which emerge after birth at age 2 to 5 years (range, 1-15 years). Rarer B-ALL subtypes, characterized by KMT2A (MLL) translocations, are also generated in utero as evidenced by similar studies. [6][7][8]

Mixtures of endocrine disrupters relevant for human exposure was found to elicit persistent effects on the rat prostate following perinatal exposure, suggesting that human perinatal exposure to environmental chemicals may increase the risk of prostate cancer later in life.

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Summary This paper evaluates in vivo predictability of a battery of in vitro tests

Adenosine triphosphate (ATP) is known to induce cell death in T lymphocytes at high extracellular concentrations. CD4+ and CD8+ T lymphocytes have a differential response to ATP, which in mice is due to differences in the P2X7 receptor expression levels. By contrast, we observed that the difference in human CD4+ and CD8+ T lymphocyte response toward the synthetic ATP-analog BzATP is not explained by a difference in human P2X7 receptor expression. Rather, the BzATP-induced human P2X7 receptor response in naïve and immune-activated lymphocyte subtypes correlated with the expression of another ATP-binding receptor: the human P2Y11 receptor. In a recombinant expression system, the coexpression of the human P2Y11 receptor counteracted BzATP-induced human P2X7 receptor-driven lactate dehydrogenase release (a marker of cell death) and pore formation independent of calcium signaling. A mutated non-signaling human P2Y11 receptor had a similar human P2X7 receptor-inhibitory effect on pore formation, thus demonstrating that the human P2X7 receptor interference was not caused by human P2Y11 receptor signaling. In conclusion, we demonstrate an important species difference in the ATP-mediated cell death between mice and human cells and show that in human T lymphocytes, the expression of the human P2Y11 receptor correlates with human P2X7 receptor-driven cell death following BzATP stimulation.

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