Expression of heparanase gene in Egyptian acute leukemia patient

Heparanase is an endoglycosidase that degrades heparin sulfate, the main polysaccharide constituent of the extracellular matrix and basement membrane. Expression of the heparanase gene is associated with the invasive, angiogenic, and metastatic potential of diverse malignant tumors and cell lines. to investigate possible relation/correlation between Heparanase gene expression and quantitation in pediatric Acute leukemia patients and clinicopathologic variables as well as patients outcome in an attempt to determine it's prognostic value and the possibility of using it as a new target for treatment. Forty pediatric acute leukemia patients [20 acute myeloid leukemia [AML] and 20 acute lymphoblastic leukemia [ALL] as well as 11 normal volunteers were analyzed for the expression and level of Heparanase gene using real time quantitative reverse transcriptase polymerase chain reaction [RTQ-PCR] to investigate a possible relation, association, or correlation with the clinical and laboratory features of patients at diagnosis, and patient outcome after treatment and follow up. Comparing the 3 groups as regards the Heparanase gene level there was high statistical significant difference [p<0.001] being maximum in AML and minimum in controls, with mean Relative quantitation [RQ] level 2336.2 +/- 10405.2 in AML ,median 8.0 and range [3.1-46543.0], while mean RQ in ALL was 1.7 +/- 1.0 ,median 1.7 and range [0.1-3.1] and in controls mean was 0.8+/-0.3, median 0.8 and range [0.4-1.4].Comparison between each 2 groups as regards heparanase level was of high statistically significant difference, p value being [p<0.001] when comparing AML/ALL and AML/controls and [p=0.035] when comparing ALL/controls. Cut off value for heparanase gene was calculated using Roc curve and was found to be 1.413 with 80% sensitivity and 100% specificity. According to this cut off level, 20/20 [100%] AML cases were heparanase positive, 12/20 [60%] [[ALL] cases were heparanase positive and 8/20 ALL patients were negative, while all controls [100%] were negative. This was of high statistical significance [p<0.001]. Comparing the overall survival [OS] of AML/ALL there was no statistically significant difference [p=0.2916], while comparing the disease free survival [DPS] of AML/ALL was of statistical significant difference [0.0312]. Comparing the final status of the disease [complete remission [CR]/ progressive disease [PD] or death] as regards the heparanase gene level RQ, showed a high statistical significant difference [p<0.005] with the level being higher in patients with PD/death. There was no significant correlation between all group and heparanase gene level as regards age, TLC, hemoglobin, platelets and peripheral blood blasts [p=0.353,0.704,0.844,0.54 and 0.097] respectively, while there was significant negative correlation on comparing bone marrow blast% and heparanase gene level [r=-0.408 and p=0.09]. Heparanse gene is expressed in acute leukemia being higher in AML than ALL and controls. Patients with higher heparanase gene showed poorer outcome. These findings suggest that heparanase gene may be a novel significant therapeutic target for acute leukemia

novel insight to the functional role of stathmin 1 in IgE-mediated activation of RBL-2H3 cells

IgE-mediated cell signaling, induced by cross-linking of high affinity receptor for IgE [FepsilonRI] in the presence of antigen [Ag], is a well known mechanism described for mast cell activation in allergy and hypersensitivity reactions, which induces a spectrum of cellular responses such as secretion and up-regulation of cell surface FepsilonRL Although for several years IgE binding to FepsilonRI was considered to be a passive sensitization process, the outcomes of several recent studies have revealed a variety of different cellular responses to IgE binding compared to IgE plus Antigen binding. The present study applied a functional proteomics-based approach to investigate mast cell signaling events and provided new insights to FcsRI-mediated cell signaling in RBL-2H3.1 cells, and may point to the activation of alternative signaling pathways in response to IgE or IgE plus Ag. Comparative analysis by 2-D PAGE of RBL cells activated with IgE plus Ag for three and four hours compared to non-activated cells was followed by mass spectrometric protein identification and provided evidence for the induction of Stathmin 1 [STMN1] gene expression in response to IgE plus Ag activation. Complementary SDS-PAGE analysis showed a distinct up-regulation of STMN1 induction in response to challenge with IgE plus Ag compared to sensitization with IgE only. Phosphoproteomics analysis gave evidence for significant increase at phosphorylation of STMN1 on ser16 after 1min, though a slight rise at 5 min, and on ser38 after 1 and 5min sensitization with IgE and a similar result was observed for 1min IgE plus Ag-activation. IgE plus Ag-activation was also found to induce the phosphorylation of ser38 to a greater extent than sensitization with IgE. In contrast, IgE alone was more effective than IgE plus Ag at inducing phosphorylation of ser 16. Collectively this study provides further insights into the role of Stathmin 1 in FepsilonRI-mediated activation of cells of mast cell lineage and might shed light on the diverse response of these cells to IgE or IgE plus Ag

Acute basophilic leukaemia: a case report.

Acute basophilic leukaemia is an uncommon form of acute leukaemia, rarely occurring as de novo disease. Due to rarity of the disease, consistent diagnostic criteria for the identification of this entity still remain the topic of discussion. Immunophenotypic profile, electron microscopy and cytogenetic analysis in addition to morphological features, are said to be highly desirable for correct identification of this entity. In set-up like ours, where such facilities are either not available or not in reach of the patients due to financial constraints, morphological features and simple technique like demonstration of metachromasia in blasts with toluidine blue stain remain the most useful diagnostic tool for identification of this rare condition. We present a case of acute basophilic leukaemia with (11q23)-MLL gene rearrangement, in an 18-year-old male with review of literature and discussion of diagnostic criteria.

Leukemid Associated with Acute Basophilic Leukemia / 대한피부과학회지

Cutaneous manifestations in leukemia present an important diagnostic challenge to dermatologists. The skin lesions can be classified as either specific or non specific. Lesions that are the direct result of infiltration and proliferation of leukemic cells in the skin are known as "specific lesions" or "leukemia cutis". Leukemic infiltration of the skin occurs in 3% to 11% of patients with adult leukemia. Non specific lesions(leukemids) occur in approximately 30% of patients with leukemia. Acute basophilic leukemia(ABL) is a rare disorder characterized by many mature and immature basophils in the blood, marrow, and other organs. This type of leukemia has not been included in the French-American-British(FAB) classification. The frequency of specific or non specific skin lesions associated with ABL has not been reported. We report herein a case of leukemid with various skin manifestations associated with ABL.

Leucemia basofílica: manifestaciones cutáneas tardías, estudio de autopsia: revisión de literatura / Basophylic leukemia: autopsy case with late cutaneus manifestations, literatura review

Presentamos una paciente de 41 años, portadora de leucemia mastocitaria, sin antecedentes previos de leucemia mieloide crónica, ni manifestaciones cutáneas iniciales. La enfermedad estaba asociada a una tuberculosis peritoneal y hepática, que curó espectacularmente. La enfermedad principal se complicó con la aparición de lesiones cutáneas viscerales y ganglionares. Se trató con inhibidores de degranulación de mastocitos sin ningún resultado. El cuadro se agravó con aparición de tumores cutáneos, urticaria, diarrea intratable y severo deterioro. La autopsia reveló: mastocitosis generalizada en ganglios linfáticos, hígado, brazo, pulmones, médula ósea y piel. En el corazón y riñones se demostró aspergilosis marcada

Acute basophilic leukemia: a case report / 대한혈액학회지

No abstract available.