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Acute myeloid leukaemia (AML) is a blood cancer with a heterogeneous genomic landscape. This study aimed to mine bioinformatics data generated by RNA sequencing to unveil an AML case transcriptome profile and identify novel therapeutic targets and markers. In this study, we have determined the transcriptomic profile and analysed gene variants of an AML patient at the time of diagnosis and validated some genes by quantitative reverse transcriptase polymerase chain reaction. ADAMTS14, ARHGAP22, and ependymin-related protein 1 (EPDR1) were markedly upregulated compared to the corresponding control. In addition, novel exonic single-nucleotide and insertion/deletion variants were identified in these genes. Hence, ADAMTS14, ARHGAP22, and EPDR1 can be proposed as potential novel targets in AML, and their exact roles should be further explored.

Rho GTPases are a class of G-proteins involved in several aspects of cellular biology, including the regulation of actin cytoskeleton. The most studied members of this family are RHOA and RAC1 that act in concert to regulate actin dynamics. Recently, Rho GTPases gained much attention as synaptic regulators in the mammalian central nervous system (CNS). In this context, ARHGAP22 protein has been previously shown to specifically inhibit RAC1 activity thus standing as critical cytoskeleton regulator in cancer cell models; however, whether this function is maintained in neurons in the CNS is unknown. Here, we generated a knockout animal model for arhgap22 and provided evidence of its role in the hippocampus. Specifically, we found that ARHGAP22 absence leads to RAC1 hyperactivity and to an increase in dendritic spine density with defects in synaptic structure, molecular composition, and plasticity. Furthermore, arhgap22 silencing causes impairment in cognition and a reduction in anxiety-like behavior in mice. We also found that inhibiting RAC1 restored synaptic plasticity in ARHGAP22 KO mice. All together, these results shed light on the specific role of ARHGAP22 in hippocampal excitatory synapse formation and function as well as in learning and memory behaviors. [ABSTRACT FROM AUTHOR]

Background Little is known about the contribution of ARHGAP22 polymorphism to diabetic retinopathy (DR) risk. We performed a case-control study to investigate the associations between ARHGAP22 and the risk of DR in a Chinese Han population. Methods A total of 341 patients with type 2 diabetes mellitus (T2DM) were selected. All patients underwent a complete eye examination. Based on this, the patients with T2DM were divided into two subgroups: 188 patients with DR and 153 patients without DR. Five single nucleotide polymorphism (SNPs) were selected and genotyped using the MassARRAY method (Sequenom, San Diego, CA, USA). The odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age and sex. Results Two susceptibility SNPs in ARHGAP22 were found to be associated with an increased risk of DR both before and after the adjustment: rs10491034 under the dominant model (adjusted OR = 0.51, 95% CI = 0.27-0.95, p = 0.032) and additive model (adjusted OR = 0.47, 95% CI = 0.26-0.84, p = 0.0098) and rs3844492 under the codominant model (adjusted OR = 3.14, 95% CI = 1.10-9.01, p = 0.023) and recessive model (adjusted OR = 3.52, 95% CI = 1.26-9.85, p = 0.011). Conclusions Our findings reveal a significant association between SNPs in the ARHGAP22 gene and DR risk in a Han Chinese population. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Circulating endothelial progenitor cells (EPCs) are derived from bone marrow and are characterized by pathological retinal neovascularization. Rho GTPase Activating Protein 22 ( ARHGAP22 ) is a DR susceptibility gene that interacts with its downstream regulatory protein ras-related C3 botulinum toxin substrate 1 (Rac1), to assist in endothelial cell angiogenesis and increasing capillary permeability. The aim of this study was to elucidate the relationship between ARHGAP22 expression and EPC levels in type 2 diabetes (T2D) patients with DR. Fifty T2D patients with DR were recruited. Circulating EPCs were characterized as CD31 + /vascular endothelial growth factor-2 + /CD45 dim /CD133 + and were quantified using triple staining flow cytometry. Real-time polymerase chain reaction tests were used to quantify ARHGAP22 expression. We found that T2D patients with proliferative DR had significantly lower EPC levels than those with non-proliferative DR ( P = 0.028). T2D patients with EPC levels above the median value (> 4 cells/10 5 events) had higher levels of ARHGAP22 expression ( P = 0.002). EPC levels were positively correlated with ARHGAP22 expression ( r = 0.364, P = 0.009). Among T2D patients with DR, a higher expression of ARHGAP22 was associated with higher levels of EPCs. ARHGAP22 may be involved in the mobilization or active circulation of EPCs, thus contributing to neovascularization during DR development., Competing Interests: CONFLICTS OF INTEREST None of the authors have any financial interests to disclose.