RUNX1 variant as a genetic predisposition factor for acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common hematological malignancy among adults and is characterized by accumulation of immature myeloid cells. Different genetic factors have role in the occurrence of AML. Among different proteins, RUNX1 and BAALC are involved in the development AML. It has been shown that BAALC overexpression is a factor that indicate shorter disease free survival in a subset of AML patients. RUNX1 has been implicated in the development of breast, prostate, lung, and skin cancers. The aim of this study is determination of the prevalence of common polymorphisms in BAALC (rs6999622 and rs62527607) and RUNX1 (rs13051066 and rs61750222) in AML patients compared with healthy subjects. A total of 100 AML patients and 100 healthy control subjects were included in our study. Genomic DNA was isolated from peripheral blood and the polymorphisms were genotyped by applying ARMS and PCR-RFLP methods. Finally, data was analyzed using SPPSS software. Our results demonstrate a significant association between the RUNX1 rs13051066 and AML in the co-dominant (odd ratio = 6.66, 95% Cl = 1.85-25, p = .006) and dominant (GT + TT versus GG: odd ratio = 6.15, 95% CI = 1.73-21.87, p = .002) models. The RUNX1 rs13051066 polymorphism is associated with risk of AML in Iranian population. Future studies should consider larger sample size for assessment of RUNX1 gene polymorphisms, and employ cytogenetic and molecular analyses in AML patients from different ethnic origins.

Autophagy modulation altered differentiation capacity of CD146+ cells toward endothelial cells, pericytes, and cardiomyocytes.

BACKGROUND: To date, many attempts are employed to increase the regenerative potential of stem cells. In this study, we evaluated the hypothesis of whether an autophagy modulation could alter differentiation potency of CD146+ cells into mature pericyte, endothelial, and cardiomyocyte lineage. METHODS: In this study, CD146+cells were enriched from the human bone marrow aspirates and trans-differentiated into mature endothelial cells, pericytes, and cardiomyocytes after exposure to autophagy stimulator (50-µM Met)/inhibitor (15-µM HCQ). The protein levels of autophagy proteins were monitored by western blotting. NO content was measured using the Griess assay. Using real-time PCR assay and western blotting, we monitored the lineage protein and gene levels. Pro-inflammatory cytokine and angiocrine factors were measured by ELISA. The fatty acid change was determined by gas chromatography. We also measured exosome secretion capacity by measuring AChE activity and real-time PCR assay. RESULT: Data revealed the modulation of autophagy factors, Beclin-1, P62, and LC3 II/I ratio in differentiating CD146+ cells after exposure to Met and HCQ (p < 0.05). The inhibition of autophagy increased NO content compared to the Met-treated cells (p < 0.05). Real-time PCR analysis showed that the treatment of CD146+ cells with autophagy modulators altered the expression of VE-cadherin, cTnI, and α-SMA (p < 0.05). Met increased the expression of VE-cadherin, α-SMA, and cTnI compared to the HCQ-treated cells (p < 0.05) while western blotting revealed the protein synthesis of all lineage-specific proteins under the stimulation and inhibition of autophagy. None statistically significant differences were found in the levels of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 after autophagy modulation. Fatty acid profile analysis revealed the increase of unsaturated fatty acids after exposure to HCQ (p < 0.05). The treatment of cells with HCQ increased the levels of TNF-α and IL-6 compared to the Met-treated cells. Data revealed the increase of exosome biogenesis and secretion to the supernatant in cells treated with HCQ compared to the Met groups (p < 0.05). CONCLUSIONS: In summary, autophagy modulation could alter differentiation potency of CD146+cells which is important in cardiac regeneration.

Real-state of autophagy signaling pathway in neurodegenerative disease; focus on multiple sclerosis.

The occurrence of neurodegenerative disease is increasingly raised. From physiopathological aspect, the emergence of auto-reactive antibodies against the nervous system antigens contributes to de-myelination in Multiple sclerosis (MS). These features cause the nervous system dysfunction. The follow-up of molecular alterations could give us a real-state vision about intracellular status during pathological circumstances. In this review, we focus on the autophagic response during MS progression and further understand the relationship between autophagy and MS and its modulatory effect on the MS evolution. The authors reviewed studies published on the autophagy status in neurodegenerative disease and on the autophagy modulation in MS prognosis, diagnosis, and possible therapies. The inevitable role of autophagy was shown in the early-stage progression of MS. Due to critical role of autophagy in different stage of cell activity in nervous system, the distinct role of autophagy should not be neglected in the development, pathogenesis, and treatment of MS.

Dual biomarkers long non-coding RNA GAS5 and its target, NR3C1, contribute to acute myeloid leukemia.

Acute myeloid leukemia (AML) is a complex hematological neoplasm with poor prognosis. At present, overwhelming evidence indicates that different genetic abnormalities are relevant to the pathogenesis of AML. Nevertheless, its exact molecular mechanism is still unknown. Recently, it was reported that lncRNAs play crucial roles in tumorigenesis. But, their role in the molecular pathogenesis of AML has not been extensively explored. GAS5, one of the earliest known lncRNAs, has an essential role in the formation and progression of multiple human cancers. It was recently demonstrated that GAS5 acts as a riborepressor of the Glucocorticoid receptor) GR) and abnormal levels of GAS5 may alter response of hematopoietic cells to glucocorticoids. GAS5 can have interaction with the GR that encoded by NR3C1 gene and inhibit its transcriptional activity. To test whether the genetic variants can be associated with AML risk, we genotyped rs55829688 (T > C) polymorphism in GAS5 and three NR3C1 SNPs namely rs6195, rs41423247 and rs6189/rs6190 in a population of 100 Iranian AML patients and 100 healthy subjects. The analysis of the data showed the frequency of alleles and genotypes of rs55829688 and rs6189/rs6190 polymorphisms did not differ between patients and healthy subjects. But, rs41423247 and rs6195 demonstrated a significant correlation with AML risk. The rs6195 was associated with higher AML susceptibility in the co-dominant (OR = 4.58, 95% CI = 2.11-9.981, P < .0001), dominant (OR = 4.55, 95% CI = 2.155-9.613, P < .0001), and over-dominant (OR = 4.43, 95% CI = 2.042-9.621, P < .0001) models. Also, the rs41423247 polymorphism was associated with higher risk of AML in co-dominant (OR = 2.07, 95% CI = 1.171-4.242, P = .012) and dominant (OR = 2.47, 95% CI = 1.192-5.142, P = .010) models. Furthermore, haplotype analysis (rs41423247, rs6189.rs6190, rs6195, and rs55829688 respectively) demonstrated that GGAT, CGGT, and GGGT haplotypes were associated with higher risk of AML in the studied population (p-values = .007, 0.042 and 0.044, respectively). The present study reveals a possible role for NR3C1 in the pathogenesis of AML.

Primary pleural lymphoma of T cell origin in a paediatric patient with a focus on radiological findings - a case report and review of literature.

PURPOSE: Pleural lymphoma is a medical condition characterised by shortness of breath and obscure chest pain, which may be a diagnostic challenge, especially when it occurs in children. Plain chest X-rays and computed tomography (CT) scan are the main imaging techniques and are the initial diagnostic methods utilised. CASE REPORT: A four-year-old boy was admitted to the emergency ward with pain in the right thoracoabdominal region, which had persisted for two months. Physical examination revealed reduced respiratory sounds in the right chest, but with no other significant findings. The patient underwent chest X-ray and CT scan, which showed right sided pleural thickening coupled with a massive pleural effusion. The patient underwent pleural biopsy, and a diagnosis of T-cell primary pleural lymphoma was made. The patient underwent treatment with BFM-NHL and was followed for three years, during which the patient remained disease free. CONCLUSIONS: Pleural lymphoma is a rare diagnosis especially in children and could have overlapping clinical manifestations with more common conditions. Imaging techniques are the main route of clinical work-up towards final diagnosis. Here, we present a rare paediatric patient with no significant past medical history, who underwent imaging and was diagnosed with T-cell primary pleural lymphoma, a very rare subtype of primary pleural lymphoma.

Chronic Exposure of Human Endothelial Progenitor Cells to Diabetic Condition Abolished the Regulated Kinetics Activity of Exosomes.

By virtue of lifestyle change, incidence of diabetes mellitus type 2 is increasingly being raised with different up-surging pathologies. It was showed that endothelial progenitor cells (EPCs) were disqualified in neo-angiogenesis induction. Besides, to an aborted differentiation property, malfunctioned paracrine activities worsen off vascular abnormality. Nano-scaled exosomes play essential roles in reciprocal cell-cell crosstalk via bioactive molecules. To address the effect of diabetic serum on exosome secretion capacity, EPCs were exposed to diabetic condition for seven days. In addition to in-vitro tubulogenesis, migration and LDL uptake assessment, exosome release capacity, and expression profiles of three genes participating in exosome kinetics, including CD63, Alix and Rab27a, revealed by Real-time PCR method. Data showed diabetic sera not only abolished the in-vitro tubulogenesis, migration and LDL uptake properties but also decreased exosome release and expression of related genes. This study sheds lights on the adverse effect of diabetic condition on exosome kinetics in EPCs.

Primary Pulmonary Fibrosarcoma With Bone Metastasis: a Successful Treatment With Post-Operation Adjuvant Chemotherapy.

INTRODUCTION: Pulmonary fibrosarcoma has been an extremely rare tumor in children. Wide surgical resection of infantile fibrosarcoma would be the treatment of choice. CASE PRESENTATION: Post-operative chemotherapy has shown the benefit in the cases of residual disease after initial surgery and metastatic disease in the literature. We have presented the case of a 70-days old male child with primary infantile fibrosarcoma of the left lung and distant metastasis of skull. CONCLUSIONS: The aim of this publication was to highlight the role of adjuvant chemotherapy to improve outcome of infantile fibrosarcoma with residual tumor and / or metastatic disease.