In the recent past, TRP (Transient Receptor Potential) channels have been
emerging as promising therapeutic targets to treat different disease conditions. In
mammals, 28 TRP channel genes have been reported. TRP channels are nonselective
cation channels that respond to different exogenous stimuli, including certain
chemicals, osmotic stress, temperature change, etc. Until now, studies on TRP channels
in relation to blood disorders are only a handful. Recently, several TRP channels have
emerged as potential contributors to different hematological disorders, including blood
iron deficiency (TRPML), hereditary hypertension (TRPC3) and blood pressure (BP)
regulation (TRPM4). Dysregulated activation of several TRP channel family members
has been reported in sickle cell disease (SCD) and in the transgenic mouse model of
SCD. In this regard, TRPV1 and TRPA1 channels have been identified as major
contributing factors in the rodent SCD pain. Erythropoietin (Epo), a glycated cytokine,
secreted by the kidney, plays an important role in red blood cell (RBC) synthesis
(erythropoiesis). In murine RBCs, Epo was found to cause TRPC4/TRPC5-mediated
calcium entry that certainly appears interesting in order to understand the roles of TRP
channels in erythropoiesis. Present evidence indicates functional roles of several TRP
channels (TRPC3, TRPC6, TRPV1, TRPV3, TRPV4, TRPA1, TRPM6 and TRPM7) in
the progression and/or prevention of fibroproliferative disorders in vital visceral organs
including blood vessels and emerges as the main contributor towards several
inflammatory processes. TRPV1 channel has gained attention as a required step for Tcell
receptor activation by mitogens. Studies involving cell lines derived from
hematological and other malignancies indicate TRPV1 could be a potential target for
novel cytotoxic therapies. Altered functional roles of several TRP channels have been
identified in different classes of hematological malignancies, including leukemias,
multiple myelomas (MM) and B-and T-cell lymphomas. TRP channels are the
modulators of the hematopoietic cells and control cellular proliferation, differentiation
and apoptosis. Thus, TRP channels appear to be promising targets for hematologic
cancer therapy and those channels warrant further investigations for novel
pharmaceutical and clinical strategies. TRPC1ε has been recently reported as preosteoclasts
and important functional roles of TRPC1ε in recruiting a subpopulation of
circulating mononuclear cells from blood to bone surface have been described in
relation to cellular differentiation. Epigenetic changes in TRPA1 promoter methylation in white blood cells (WBC) have been identified as predictive of human thermal pain
sensitivity. An inverse relationship exists between TRPV1 and TRPA1 gene expression
in peripheral blood cells with increasing pain symptoms. This chapter reviews different
TRP channel expressions in blood cells with a focus on recent advancements of
understanding TRP channels as potential therapeutic targets in different blood
disorders. This chapter also briefly discusses a few TRP channel modulator drugs that
had shown promising results in preclinical studies or in clinical trials. For the sake of
simplicity and to stay focused on the present issue of the journal, this chapter briefly
discusses the functional roles of some TRP channel proteins that have been emerging
as possible drug targets to treat some blood disorders and hematological malignancies.
Keywords: Blood Disorders, Ca2+ signaling, Hematological Malignancies, TRP
Channels.
