Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

Abstract

T leukemogenesis is a multistep process, where the genetic errors during T cell maturation cause the healthy progenitor to convert into the leukemic precursor that lost its ability to differentiate but possesses high potential for proliferation, self-renewal, and migration. A new misdirecting “leukemogenic” signaling network appears, composed by three types of participants which are encoded by (1) genes implicated in determined stages of T cell development but deregulated by translocations or mutations, (2) genes which normally do not participate in T cell development but are upregulated, and (3) nondifferentially expressed genes which become highly interconnected with genes expressed differentially. It appears that each of three groups may contain genes coding ion channels. In T cells, ion channels are implicated in regulation of cell cycle progression, differentiation, activation, migration, and cell death. In the present review we are going to reveal a relationship between different genetic defects, which drive the T cell neoplasias, with calcium signaling and ion channels. We suggest that changes in regulation of various ion channels in different types of the T leukemias may provide the intracellular ion microenvironment favorable to maintain self-renewal capacity, arrest differentiation, induce proliferation, and enhance motility.

A multiplatform strategy for the discovery of conventional monoclonal antibodies that inhibit the voltage-gated potassium channel Kv1.3

“…Jurkat cells are a human leukemia T-cell line that has been reported to express ∼ 200 active Kv1.3 ion channels per cell. 32 Of 41 antibodies tested, Jurkat cell binding was detected with 6 antibodies (ch_p1A11, ch_p1H7, ch_p1D8, ch_p1E6, ch_p2A3 and ch_p2G9) comprising a range of median fluorescence intensity of 1157 to 9401 compared to an average MFI of 198 +/− 41 ( n = 35) for all other antibodies analyzed.…”

Functional Role of MicroRNAs in Thymocyte Development

“…T lymphocytes, referred to as T cells, are derived from the early T-lineage precursor of the bone marrow or embryonic liver lymphoid stem cells, which develop and mature in the thymus and then migrate into peripheral immune organs or tissues to perform their biological functions [1-3]. During the development of the thymus, T cells can be divided into 3 stages based on the differential expression of CD4 and CD8 coreceptors (Fig.…”

Differential Activity of Voltage- and Ca2+-Dependent Potassium Channels in Leukemic T Cell Lines: Jurkat Cells Represent an Exceptional Case

“…Indeed, many of the findings in this field were made with Jurkat cell line as the T cell in vitro model and then extrapolated to healthy T cells ( Abraham and Weiss, 2004 ). With time, many researchers questioned the physiological relevance of such approach, because a number of differences in comparison to healthy cells were demonstrated for Jurkat cells (reviewed by Dobrovinskaya et al, 2015 ).…”