scholarly journals Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Hussein Ghamlouch ◽  
Eileen M. Boyle ◽  
Patrick Blaney ◽  
Yubao Wang ◽  
Jinyoung Choi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Genetic Basis ◽  
Aberrant Expression ◽  
Phd Finger ◽  
Polycomb Repressive Complex 2 ◽  
Histone 3 ◽  
Cell Growth And Differentiation ◽  
And Function

AbstractDespite  improvements in outcome, 15-25% of newly diagnosed multiple myeloma (MM) patients have treatment resistant high-risk (HR) disease with a poor survival. The lack of a genetic basis for HR has focused attention on the role played by epigenetic changes. Aberrant expression and somatic mutations affecting genes involved in the regulation of tri-methylation of the lysine (K) 27 on histone 3 H3 (H3K27me3) are common in cancer. H3K27me3 is catalyzed by EZH2, the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). The deregulation of H3K27me3 has been shown to be involved in oncogenic transformation and tumor progression in a variety of hematological malignancies including MM. Recently we have shown that aberrant overexpression of the PRC2 subunit PHD Finger Protein 19 (PHF19) is the most significant overall contributor to HR status further focusing attention on the role played by epigenetic change in MM. By modulating both the PRC2/EZH2 catalytic activity and recruitment, PHF19 regulates the expression of key genes involved in cell growth and differentiation. Here we review the expression, regulation and function of PHF19 both in normal and the pathological contexts of solid cancers and MM. We present evidence that strongly implicates PHF19 in the regulation of genes important in cell cycle and the genetic stability of MM cells making it highly relevant to HR MM behavior. A detailed understanding of the normal and pathological functions of PHF19 will allow us to design therapeutic strategies able to target aggressive subsets of MM.

CD38 as an immunomodulator in cancer

2020 ◽  
Vol 16 (34) ◽  
pp. 2853-2861
Author(s):  
Yanli Li ◽  
Rui Yang ◽  
Limo Chen ◽  
Sufang Wu
Keyword(s):  
Multiple Myeloma ◽  
Cell Activation ◽  
Human Tissues ◽  
Transmembrane Glycoprotein ◽  
Cell Activation Marker ◽  
Research Findings ◽  
A Cell ◽  
And Function ◽  
Human Molecule

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

scholarly journals HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fengjie Jiang ◽  
Xiaozhu Tang ◽  
Chao Tang ◽  
Zhen Hua ◽  
Mengying Ke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Aberrant Expression ◽  
The Stability ◽  
Induced Apoptosis ◽  
Proliferation In Vitro

AbstractN6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.

scholarly journals Chromatin Enrichment for Proteomics in Plants (ChEP-P) Implicates the Histone Reader ALFIN-LIKE 6 in Jasmonate Signalling

2021 ◽  
Author(s):  
Isabel Cristina Vélez-Bermúdez ◽  
Wolfgang Schmidt
Keyword(s):  
Histone Variants ◽  
Homeodomain Protein ◽  
Chromatin Dynamics ◽  
Histone 3 ◽  
Plant Homeodomain ◽  
Associated Proteins ◽  
Bona Fide ◽  
Covalent Modifications ◽  
And Function

Abstract BackgroundCovalent modifications of core histonesgoverndownstream DNA-templated processes such as transcription by altering chromatin structure and function. Previously, we reported that the plant homeodomain protein ALFIN-LIKE6 (AL6), a bona fide histone reader that preferentially binds trimethylated lysin 4 on histone 3 (H3K4me3), is critical for recalibration of cellular phosphate (Pi) homeostasis and root hair elongation under Pi-deficient conditions. ResultsHere, we demonstrate that AL6 is also involved in the response of Arabidopsis seedlings to jasmonic acid (JA) during skotomorphogenesis, possibly by modulating chromatin dynamics that affect the transcriptional regulation of JA-responsivegenes. Dark-grown al6 seedlings showed a compromised reduction in hypocotyl elongation upon exogenously supplied JA, a response that was calibrated by the availability of Pi in the growth medium. A comparison of protein profiles between wild-type and al6 mutant seedlings using a quantitative Chromatin Enrichment for Proteomics (ChEP) approach,that we modified for plant tissue and designated ChEP-P (ChEP in Plants), yielded a comprehensive suite of chromatin-associated proteins and candidates that may be causative for the mutant phenotype. ConclusionsAltered abundance of proteins involved in chromatin organization in al6 seedlings suggests a role of AL6 in coordinating the deposition of histone variants upon perception of internal or environmental stimuli. Our study shows that ChEP-P is well suited to gain holistic insights into chromatin-related processes in plants. Data are available via ProteomeXchange with identifier PXD026541.

scholarly journals Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience

Blood ◽  
2015 ◽  
Vol 125 (13) ◽  
pp. 2095-2100 ◽  
Author(s):  
Benjamin Hebraud ◽  
Florence Magrangeas ◽  
Alice Cleynen ◽  
Valerie Lauwers-Cances ◽  
Marie-Lorraine Chretien ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Prognostic Value ◽  
Key Points ◽  
Chromosomal Changes

Key Points Additional chromosomal changes modulate the outcome of patients with high-risk multiple myeloma.

scholarly journals Significance of Modified Risk Stratification Msmart 3.0 and Autologous Stem Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5593-5593
Author(s):  
Andrey Garifullin ◽  
Sergei Voloshin ◽  
Vasily Shuvaev ◽  
Irina Martynkevich ◽  
Elizaveta Kleina ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Group ◽  
High Risk Group ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Genetic Abnormalities ◽  
Standard Risk

Background The risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies and other factors. The most extensive and modern system in this time is mSMART risk stratification involving many parameters such as genetic anomalies, albumin, beta-2-microglobulin, LDH, Plasma Cell S-phase and GEP levels. It is possible to use risk-adapted treatment programs with or without ASCT. Nevertheless, the role of complex karyotype, combination of genetic abnormalities and ASCT remains unclear. Aims To estimate the genetic abnormalities in patients with newly diagnosed multiple myeloma and define the role of risk-stratification and ASCT in prognosis of disease. Methods The study included 159 patients (median age 63 years, range 28 - 83; male: female ratio - 1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). ASCT was performed at 42% patients. Results The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) - 16.3% (26/159), t(4;14) - 5.0% (8/159); TP53/del17p - 5.6% (9/159); 1p32/1q21 amp/del - 12% (19/159); hypodiploidy - 3.1% (5/159); hyperdiploidy - 1.25% (2/159); del5q - 0,6% (1/159); other - not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (>3 aberrations) - in 4.4% (7/159) patients. The median OS in "two aberration" and "complex abnormalities" groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 26 months and was not reached, respectively (p=.00015). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p=.011). Differences between "two aberration" and "complex abnormalities" groups were not find (p> .05). We modified high-risk (gain 1q, p53 mutation, del 17p deletion, t(4;14), t(14;16), t(14;20), R-ISS stage III, double and triple hit myeloma) mSMART 3.0 by adding "two aberration" and "complex abnormalities" groups on based the OS and PFS results. The final analysis was based on the results of the complex examination of 87 patients: 53 patients in standard-risk group and 34 patients in high-risk group. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0mod - 48 months; 5-years OS was 62% and 38%, respectively (p=0.0073). The median PFS was 43 and 29 months, respectively (p=.09). The best results of OS and PFS were reach in both groups of patient who performed ASCT. The median OS in standard-risk mSMART 3.0 with ASCT (n=37) was not reached, in high-risk mSMART 3.0mod with ASCT - 48 months (n=20); standard-risk mSMART 3.0 without ASCT - 40 months (n=16); in high-risk mSMART 3.0mod without ASCT - 22 months (n=14); 5-years OS was 81%, 60%, 33% and 28%, respectively (p=0.0015). The median PFS was not reached, 46, 22 and 19 months, respectively (p=.017). Conclusions The combination of two aberrations and complex abnormalities is unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk group according mSMART 3.0mod. The ASCT can improve treatment's outcomes and life expectancy especially in patients with high-risk. It can be useful for update risk stratification in a future. Disclosures Shuvaev: Novartis: Consultancy; Pfize: Honoraria; Fusion Pharma: Consultancy; BMS: Consultancy.

MiR-15a and Mir-16-1 Affects the Angiogenesis of Multiple Myeloma by Targeting VEGF-A

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4039-4039
Author(s):  
Chunyan Sun ◽  
Yu Hu ◽  
Xiaomei She ◽  
Zhangbo Chu ◽  
Jun Fang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Conditioned Medium ◽  
Cell Lines ◽  
Tumor Volume ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Transfected Cells ◽  
Average Tumor Volume ◽  
Rpmi 8226

Abstract Abstract 4039 MicroRNAs (miRNAs) are non-coding small RNAs that negatively modulate protein expression at a post-transcriptional level and are deeply involved in the pathogenesis of a variety of cancers. Two miRNAs, miR-15a and miR-16, which act as putative tumor suppressor by targeting the oncogene BCL2, have been implicated in cell cycle, apoptosis and proliferation. Here we investigated the possible role of miR-15a/miR-16 in the angiogenesis of multiple myeloma (MM). Using stem-loop quantitative reverse transcription-PCR analysis, we showed that miR-15a/miR-16 are significantly underexpressed in primary MM cells as well as MM cell lines (RPMI 8226, ARH-77, OPM-2, KM3, U266 and NIH929). The aberrant expression of miR-15a/miR-16 were detected especially in advanced stage multiple myeloma. The expression of miR-15a and miR-16-1 were remarkably lower in stage III MM patients (n=23), whereas it were significantly higher in healthy individuals (n=18) and stage 2, II MM patients (n=14) (P<0.01 and P<0.001, respectively). In human MM cell lines and normal plasma cell, expression of miR-15a/miR-16 inversely correlated with the expression of vascular endothelial growth factor (VEGF). Consistently with the proposed role of miRNAs as key regulators of angiogenesis, here we identified VEGF-A as a target for miR-15a and -16. Enforced miR-15a or miR-16 expression reduced VEGF-A protein level and the luciferase reporter assays demonstrated that miR-15a and -16 specifically suppress expression of VEGF-A by directly interacting with its 3′-untranslated region. Moreover, Ectopic overexpression of miR-15a and -16 led to decreased pro-angiogenic activity of MM cells. Conditioned medium of pri-miR-15a- and pri-miR-16- transfected RPMI 8226 cells inhibited human bone marrow microvascular endothelial cell (BMEC-1) proliferation, chemotactic motility and capillary formation in vitro as compared with conditioned medium of scramble probe-transfected RPMI 8226 cells (P<0.05). Finally, miR-15a/miR-16 was shown to greatly inhibit the process of tumor formation in an animal model. Infection of lentivirus-miR-15a or lentivirus-miR-16 can significantly inhibit the xenograft tumor growth in nude mice. The average tumor volume after 4 weeks for GFP-transfected cells was 372.5 mm3. While the average tumor volume for miR-15a-transfected cells was 47 mm3 (P<0.05) and for miR-16-transfected cells was 93.6 mm3 (P<0.05). Of interest, neoangiogenesis analysis by immunohistochemistry staining of anti-CD31 showed that there were significant reductions in microvessel density present in the miR-15a group and miR-16 group as compared to control (P<0.05). Take together, our findings suggested that miR-15a and miR-16 could play a role in the tumorigenesis of MM at least in part by modulation of angiogenesis through targeting VEGF-A. These findings have therapeutic implications and may be exploited for future treatment of MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Daratumumab in untreated newly diagnosed multiple myeloma

2019 ◽  
Vol 10 ◽  
pp. 204062071989487 ◽  
Author(s):  
Nadine Abdallah ◽  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Clinical Trials ◽  
High Risk ◽  
Human Monoclonal Antibody ◽  
Proteasome Inhibitors ◽  
Immunomodulatory Drugs ◽  
Newly Diagnosed ◽  
Infusion Reactions

The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.

scholarly journals Prognostic role of circulating exosomal miRNAs in multiple myeloma

Blood ◽  
2017 ◽  
Vol 129 (17) ◽  
pp. 2429-2436 ◽  
Author(s):  
Salomon Manier ◽  
Chia-Jen Liu ◽  
Hervé Avet-Loiseau ◽  
Jihye Park ◽  
Jiantao Shi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Survival Prediction ◽  
Prognostic Role ◽  
High Risk Factors ◽  
Key Points ◽  
Exosomal Mirnas

Key Points Two circulating exosomal microRNAs, let-7b and miR-18a, improved survival prediction in patients with MM. Circulating exosomal miRNAs enhanced the stratification of patients with high-risk factors.

scholarly journals Role of High-Dose Melphalan and Autologous Stem Cell Transplantation in Multiple Myeloma Patients Presenting with t(11;14)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4580-4580 ◽  
Author(s):  
Eduardo Sobejano ◽  
Veronica Gonzalez De La Calle ◽  
Victor Higuero ◽  
Fernando Escalante ◽  
Ramón García-Sanz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
University Hospital ◽  
First Line ◽  
Advisory Committees ◽  
Baseline Characteristics ◽  
Standard Risk

INTRODUCTION The t (11; 14) by fluorescent in situ hybridization (FISH) is found in 15-20% of patients with multiple myeloma (MM) . Although it was classically considered a standard risk translocation or even a good prognosis, recent studies conducted in the era of new drugs show contradictory results and it is not well established if they have to be considered intermediate or standard risk. The possibility of using targeted therapy with venetoclax for patients harboring t(11;14) makes the investigation of the outcome of newly diagnosed multiple myeloma (NDMM) with t(11;14) as relevant. METHODS We analyzed the baseline characteristics and outcome of patients with t(11;14)and receiving HDT-ASCT within the series of 647 patients with NDMM between 1988 and 2018 according to the current criteria at each moment at two academic hospitals in Spain (University Hospital of Salamanca and Hospital of Leon) . The FISH was performed on selected cells according to international regulations and centralized at the University Hospital of Salamanca. For this purpose, a descriptive cross-sectional study was first conducted comparing the characteristics of patients with t (11; 14) versus the rest. The final objective wasto evaluate the role of HDT-ASCT in NDMM with t(11;14). RESULTS The baseline characteristics of the whole series were: a median age of 71years (yrs) (range:30-96). 217 patients (33,5%) were under 65 years. 352 (56.2%) were IgG; 161 (25.7%) IgA; 87 (13.9%) Bence Jones; 19 (3%) non-secretors, and 5 and 2 cases were IgD and IgM, respectively. 320 (53.2%) received novel agents as part of the first line of therapy. Overall, 153 (27.8%) achieved complete response (CR) after first line, and 403 (73.1%) at least a partial response. After a median follow-up for living patients of 4.26 yrs (range: 0,1-27.3), the OS of the entire series was 2.74 years. T(11;14) was performed in 440 NDMM patients and was positive in 80 (18.2%). Only in 5 patients other high-risk alterations (t (14:16), t (4:14) or del17p (p53)) were detected. The baseline characteristics of patients with and without t (11:14) did not show significant differences, except for the heavy chain pattern(p <0,001). IgA was lower in patients with t(11:14) 12,8% (10 out of 78)vs 27,7% (98 out of 353). Of note, most patients with non-secretory MM (10 out of 16, 62,5%) had the t(11;14) whilst in the conventional secretory MM patients, t(11;14) was observed in 68out of 415(16,4%). In addition, the plasma cell bone marrow infiltration was significantly higher in patients with t(11;14)(> 60% Plasma Cells) 32.8% vs 13.3%(p <0.001)). HDT-ASCT was performed in 162 patients (25%)and 22 of them (13,5%) were positive for the t(11:14) and only in 2 patients, other high-risk alterations were detected.The induction therapy received in both treatments arms was homogeneous basically consisted on combinations of proteasome inhibitors plus immunomodulatory drugs. The median OS for NDMM patients undergoing ASCT was 4,33 years. (range: 0,47-26,85) and the median PFS for this patients was 2,25 yrs (range: 0,1-27,25) The median PFS for patients with t (11/14) undergoing ASCT trended to be higher than that observed in patients without t(11;14) who received also HDT-ASCT (99.1 vs 54.9 months), without obtaining significant results, (p 0.205) maybe due to the small number of patients (Figure 1).The median OS in the group of patients with and without t(11:14) undergoing ASCT was 120,8 vs 140 months (p= 0,829). In the cohort of non eligible ASCT patients both median PFS and OS for patients with t(11:14) was similar than that observed in patients without t(11:14)(median PFS of 19,9 vs 19,4 months) (p 0,438) and (median OS of 31,5 vs 44 months) (p 0,424), respectively. CONCLUSION T(11;14) seems to be a cytogenetic abnormality more frequently observed in patients with NDMM and non secretory phenotype what requires further investigation. Patients with t(11;14) benefit the most if they received HDT-ASCT and it would represent a therapeutic strategy of choice if the patient is transplant-eligible. Figure 1 Disclosures Puig: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; The Binding Site: Honoraria; Takeda, Amgen: Consultancy, Honoraria. Mateos:Abbvie: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; EDO: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Pathophysiological Role of K2P Channels in Human Diseases

2021 ◽  
Vol 55 (S3) ◽  
pp. 65-86
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Ion Homeostasis ◽  
Human Diseases ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
K2p Channels ◽  
And Function

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

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