Higher mTOR Expression: A Marker of Poor Outcome in Patients with de Novo AML.

Acute myeloid leukemia (AML) displays significant clinical diversity mainly due to the variation in the underlying molecular defects, which is now recognized as the main driver for leukemogenesis. mTOR deregulation is thought to promote the proliferation and survival of leukemic blasts. This work aimed to study mTOR gene expression as a prognostic marker and a potential therapeutic target in AML. Quantitative real-time PCR evaluated mTOR expression in 45 new AML cases in relation to disease characteristics and outcome. mTOR was overexpressed in AML patients and higher levels were seen in the group that was not in complete remission (CR), at the end of induction, compared to those who achieved remission (17.03 ± 16.44 vs 3.91 ± 2.55 respectively, p < 0.001). In addition, mTOR expression inversely correlated with survival (p < 0.001). Patients with mTOR expression > 5.2 had a median overall survival of 10 months as opposed to 23 months in those with an expression of ≤ 5.2, p < 0.001. mTOR was an independent risk factor for failure of response in our patient group (p 0.007 and OR 1.54). mTOR has prognostic implications as it predicted the response and survival in our patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01569-3.

Assessment of plasminogen activator inhibitor-1(PAI1) and thrombin activitable fibrinolysis inhibitor (TAFI) in Egyptian children with hemophilia A.

Patients with hemophilia A display varied bleeding phenotypes not correlated with degree of deficiency of factor VIII level. We investigated Plasminogen Activator Inhibitor 1(PAI1) level and Thrombin Activatable Fibrinolysis Inhibitor (TAFI) also known as Carboxypeptidase B2 (CPB2) level in Patients with hemophilia A and their possible correlation with bleeding tendency. Twenty-six patients attending in hematology unit of pediatric department were included in this study. In addition, fourteen apparently healthy subjects matched ages and genders were included as control group. The International Society of Thrombosis Bleeding Assessment Tool (ISTH/BAT) was used to assess bleeding score in patients. Plasma levels of Plasminogen Activator Fibrinolysis Inhibitor (PAI1) and Thrombin Activatable Fibrinolysis Inhibitor (TAFI) zymogen were measured by enzyme-linked immunosorbent assay (ELIZA). As compared to controls, hemophilic patients had significantly high bleeding score, low PAI 1 level and high TAFI level. There was no significant correlation between bleeding score by ISTH/BAT and patient severity. PAI 1 and TAFI level have no significant correlation with patient severity. PAI 1 level was statistically significant different between intense and non-intense hemorrhagic groups, while TAFI level has no significant correlation with bleeding phenotype. PAI 1 and TAFI levels had significantly correlation between patients and controls. PAI-1 level had statistically significant correlation with bleeding phenotype, while TAFI level failed to show any correlation between intense and non-intense hemorrhagic groups. So, PAI-1 levels may have predictive value of bleeding tendency in hemophiliacs.

Deregulated Expression of Long Non-coding RNA HOX Transcript Antisense RNA (HOTAIR) in Egyptian Patients with Multiple Myeloma.

Increasing evidence of involvement of non-coding RNAs, especially long non-coding RNAs (lncRNAs), in the molecular biology of various malignancies have been recently reported. Their utilization as markers for diagnosis, prognosis and evaluation of treatment response was widely investigated. As the impact of lncRNA HOTAIR on multiple myeloma (MM) was not properly highlighted, we aimed to explore the expression levels of HOTAIR in three groups of MM patients and to analyze its relationship to different patients' characteristics. Plasma samples were withdrawn from 24 newly diagnosed MM patients, 23 post-therapy patients in complete response (CR) or very good partial response (VGPR) and 15 patients who had either progressive disease (PD) or relapse. The expression of lncRNA HOTAIR in MM patients and 20 healthy controls was analyzed by quantitative reverse transcription polymerase chain reactions. HOTAIR was significantly upregulated in newly diagnosed and PD/relapse categories in comparison with controls and MM patients who had achieved CR or VGPR (P < 0.001). Furthermore; HOTAIR expression levels correlated with the percentage of malignant plasma cells in bone marrow (P = 0.006) and disease stage (ISS stage) (P = 0.031). HOTAIR may be employed as  prognostic molecular marker and novel therapeutic tool for newly diagnosed MM patients.

Influence of esophageal variceal bleeding on iron status in chronic hepatitis C patients.

BACKGROUND: Disorders of serum iron balance are frequently observed in chronic hepatitis C (CHC) patients. Iron overload as well as iron deficiency anemia are common clinical findings in these patients. Variceal bleeding is also a common complication. To date, no study has discussed the influence of esophageal bleeding on iron status in anemic CHC bleeders. OBJECTIVE: Was to study reticulocyte hemoglobin content (CHr) and serum hepcidin levels in anemic CHC and to evaluate the influence of variceal bleeding on patients' iron status. METHODS: Serum hepcidin levels and CHr were assessed in 65 early phase CHC patients (20 nonanemic, 23 anemic nonbleeders, and 22 anemic bleeders), and 20 healthy controls; and were compared with the conventional indices of iron deficiency including mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, serum iron, total iron binding capacity, transferrin saturation and ferritin. RESULTS: Hepcidin levels were comparable in patients groups, but were significantly lower in patients than in controls (P = 0.01). Child-Pugh class B patients showed significantly lower hepcidin levels than class A patients. CHr levels were comparable in all groups as well as all iron deficiency indices. Patients with ferritin values or less 100 ng/ml and CHr or less 29 pg/cell or Tfsat or less 16% are more likely to have iron deficiency [odds ratio (OR = 3.93, 95% confidence interval (CI) = 2.54-6.08; OR = 10.50, 95% CI = 1.94-56.55, respectively). CONCLUSION: Esophageal bleeding has an almost no influence on iron status in CHC patients. Serum hepcidin content is influenced by CHC disease rather than by anemia associated with or without esophageal bleeding and it could be used as a marker of early hepatic insufficiency. Assessing CHr content could add a potential utility in the detection of iron deficiency in CHC patients.