title: Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia.
abstract: Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca(2+) signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options.
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima Colima, México.
authors.forename: Oxana
authors.initials: O
authors.lastname: Dobrovinskaya
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima Colima, México.
authors.forename: Georgina
authors.initials: G
authors.lastname: Valencia-Cruz
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de ColimaColima, México; Consejo Nacional de Ciencia y TecnologíaMéxico City, México.
authors.forename: Luis
authors.initials: L
authors.lastname: Castro-Sánchez
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima Colima, México.
authors.forename: Edgar O
authors.initials: EO
authors.lastname: Bonales-Alatorre
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima Colima, México.
authors.forename: Liliana
authors.initials: L
authors.lastname: Liñan-Rico
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima Colima, México.
authors.forename: Igor
authors.initials: I
authors.lastname: Pottosin
keywords: T leukemia; T lymphocyte; acetylcholine; acetylcholinesterase; calcium signaling; choline acetyltransferase; muscarinic receptor non-neuronal cholinergic system