Clonal heterogeneity by fluorescence in situ hybridization in multiple myeloma: enhanced cytogenetic risk stratification.

Background: Multiple myeloma (MM) is a proliferation of monoclonal plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Cytogenetic analysis is a challenge in MM because of the low mitotic activity and the rapid loss of plasma cells viability in bone marrow culture. Adding mitogens such as interleukin 6 (IL6) is known to promote the in vitro growth of myeloma cell lines and enhance the fluorescence in situ hybridization application. This study aims to evaluate the prognostic impact of cytogenetic abnormalities detected by enhanced interphase fluorescence in situ hybridization (iFISH) technique in Egyptian MM patients. Results: Patients who had hyperdiploidy significantly presented with higher Hb level and lower calcium levels compared to non-hyperdiploid patients. They were staged as stage I and II by International staging system (ISS) and considered as standard risk showing better response to treatment. On the contrary, features associated with a worse outcome were patients having del 17p and those belonged to intermediate and high risk groups. Conclusion: In conclusion, adding interleukin 6 to MM cell culture promotes the in vitro growth of myeloma cells and enhances the successful application of FISH technique. A comprehensive FISH probe set investigating high, intermediate and low-risk cytogenetic abnormalities is needed for accurate risk stratification. Hyperdiploid-myeloma is a favorable risk genetic subtype of MM associated with rapid response to therapy compared to patients having del 17p, t(4;14), and other 14q rearrangements rather than t(11;14) and t(6;14).

Circulating miRNAs and tissue iron overload in transfusion-dependent ß-thalassemia major: novel predictors and follow-up guide.

Tissue iron overload is a life-threatening scenario in children with transfusion-dependent ß-thalassemia major, miRNAs that are involved in iron hemostasis could serve as therapeutic targets for control of iron overload. We aimed to find out the association between three iron-related miRNAs "miR-let-7d, miR-122, and miR-200b" and excess iron in tissues, in transfusion-dependent ß-thalassemia major patients. Circulating miRNA expressions are measured in peripheral blood (PB) samples using qPCR of transfusion-dependent (TDT) ß-thalassemia patients (n = 140) and normalized to non-transfusion-dependent (NTDT) ß-thalassemia (n = 45). Results revealed that plasma expression levels of miR-let-7d and miR-200b were significantly downregulated in TDT patients; however, miR-122 was upregulated. In terms of tissue iron load, aberrant expression of miRNAs was significantly associated with increased-iron accumulation in hepatic and cardiac tissues. We concluded that circulating miRNAs are strong candidates that associate iron hemostasis in transfusion-dependent ß-thalassemia major patients. And by extension, targeting miR-let-7d, miR-122, and miR-200 might serve as novel sensitive, specific and non-invasive predictor biomarkers for cellular damage under condition of tissue iron excess.

Comprehensive study on laboratory biomarkers for prediction and diagnosis of deep venous thrombosis.

Deep venous thrombosis (DVT) is based upon clinical suspicion in patients at risk and confirmatory duplex imaging of the deep venous system of the affected extremity. The aim of the present study was to determine different cutoff points of D-dimer, P-selectin and microparticles that could be used in early diagnosis and prediction of impending DVT in symptomatic patients with normal duplex ultrasound. Three groups of individuals were examined: 50 healthy volunteers (Group I); 75 patients with positive duplex ultrasound for DVT (Group II) and 75 symptomatic patients, but with negative duplex ultrasound for DVT (Group III). D-dimer was measured by immunoturbidimetric assay, P-selectin by flow cytometry and microparticles by ELISA. D-dimer, P-selectin and microparticles levels were significantly higher in Group II and III patients when compared with Group I individuals. Using receiver-operating characteristic curves, we determined that cutoff levels of 0.92 mg/l for D-dimer, 17.8% for P-selectin and 16.5 nmol/l for microparticles can accurately rule out DVT. New cutoff levels were estimated for the three studied biomarkers that differentiated the group of DVT-negative duplex patients without thrombosis from those patients of the same group who developed thrombosis being 2.81 mg/l for D-dimer, 30.2% for P-selectin and 26 nmol/l for microparticles. D-dimer, P-selectin and microparticles can be used to diagnose and detect impending DVT, thus identifying patients at high risk that could benefit from early anticoagulant therapy without the need for imaging studies.