FLT3 overexpression in acute promyelocytic leukemia patients without detectable FLT3-ITD or codon 835-836 mutations: a pilot study.

BACKGROUND: Activating mutations of the FLT3 receptor tyrosine kinase are common in acute promyelocytic leukemia (APL) but have uncertain prognostic significance. Information regarding FLT3 expression levels in APL without FLT3 mutations is lacking. MATERIALS AND METHODS: Using RT-PCR, mutation analysis of the FLT3 gene, regarding internal tandem duplications (ITDs) and codon 835-836 point mutations, was performed and real-time PCR was carried out to determine the level of FLT3 expression in 11 APL patients at diagnosis and 5 in haematological remission with molecularly detectable disease. RESULTS: High levels of FLT3 transcript, at least a 10-fold increase compared to the normal controls, were found at diagnosis in all 3 mutated cases and in 2 patients without detectable FLT3 mutations. CONCLUSION: FLT3 overexpression can be documented in patients without FLT3 mutations. These patients might benefit from treatment using specific FLT3 tyrosine kinase inhibitors. Larger studies are needed to evaluate the clinical and biological significance of FLT3 overexpression in the absence of FLT3 mutations.

Interleukin-18 in multiple myeloma patients: serum levels in relation to response to treatment and survival.

Interleukin-18 (IL-18) plays a role in the host's response to tumours and angiogenesis. We determined serum levels of IL-18, vascular endothelial growth factor (VEGF), angiogenin (ANG), tumor necrosis factor (TNF-alpha) and CRP in 65 newly diagnosed myeloma patients. IL-18, VEGF, angiogenin, TNF-alpha and CRP were significantly higher at stage III in comparison to stages II and I. These cytokines (measured in 27 patients) significantly decreased after treatment. In survival analysis, higher levels of IL-18 were associated with a poorer prognosis. We conclude that increased serum IL-18 in myeloma patients correlates with advanced disease, increased levels of angiogenic cytokines and worse survival.

Gastric outlet obstruction caused by a giant gastroduodenal artery aneurysm: a case report.

Gastric outlet (GO) obstruction in an adult is usually caused by intrinsic gastric or duodenal lesions or pancreatic tumours. This study describes a case of a 77-year-old man who developed GO obstruction due to extrinsic compression from a large gastroduodenal artery aneurysm under rupture. This cause of GO obstruction has never previously been reported in the literature.

Alterations of CD43 expression in transfusion-dependent myelodysplastic syndromes.

CD43 is a sialylated glycoprotein expressed on the surface of most haemopoietic cells and has been implicated in cell adhesion and signaling. It has previously been shown that CD43 expression is altered in patients with myelodysplastic syndrome (MDS). This raised the question of whether the alteration is associated with transfusions in these patients. We studied the expression of this antigen on peripheral blood leucocytes in two groups of patients with refractory anaemia, 22 transfused and 20 non-transfused. We found decreased expression of CD43 on the monocytes and neutrophils of patients receiving transfusions. Other activation molecules were studied (CD11b, CD18) and were found up-regulated suggesting the existence of activated leucocytes in these patients. The increased levels of soluble vascular cellular endothelial molecule after transfusions in these patients suggested vascular endothelial activation in the absence of infection. Given together, these results show that decreased CD43 in the transfused group of MDS patients is associated with an activated endothelial phenotype.

Activated peripheral blood and endothelial cells in thalassemia patients.

BACKGROUND AND OBJECTIVES: Thalassemia patients have alterations in the expression of some activation and adhesion molecules on peripheral blood lymphocytes. We studied cell surface antigens on peripheral blood cells associated with the activation of these cells and soluble molecules produced by activated endothelium. DESIGN AND METHODS: We investigated the expression of CD11b, CD18, CD35, CD43, CD44, and CD69 on the peripheral blood monocytes, Cd11b, CD18, CD35, CD43, CD44, CD67 on peripheral blood neutrophils and CD38 and CD69 on peripheral blood lymphocytes. We studied 68 transfusion-dependent thalassemics (group A), 10 transfusion non-dependent thalassemics (group B), 18 beta-thalassemia carriers (group C), and 28 normal individuals. Relative fluorescence intensity was used to determine the antigen density. Analysis was performed with an EPICS ELITE flow cytometer. Furthermore, soluble intercelullar adhesion molecule 1 (sICAM-1), soluble vascular adhesion molecule 1 (sVCAM-1), and E-selectin, tumor necrosis factor (TNF) alpha, and interleukin (IL) 1beta were measured in the plasma of patients by enzyme-linked immunometric assay. RESULTS: The expression of CD11b, CD18, and CD69 on the monocytes of group A was significantly greater than in groups B and C and in controls, while CD44 was significantly downregulated in group A. CD11b, CD18, CD35, CD44, and CD67 on the surface of neutrophils and CD38 and CD69 on the surface of lymphocytes were also overexpressed in group A. CD44 was downregulated on the monocytes and upregulated on the neutrophils of the patients compared to controls. The levels of sICAM-1, sVCAM-1, E-selectin, TNF-alpha, and IL-1beta in the serum of patients in groups A and B were higher than those in group C and the controls. CONCLUSION: Endothelial activation markers are significantly increased in thalassemia patients, and activated blood cells circulate in the peripheral blood. These may be related to the vascular complications in these patients and might be useful markers for the follow-up of the vascular disease.

Aberrant expression of the major sialoglycoprotein (CD43) on the monocytes of patients with myelodysplastic syndromes.

CD43, a sialylated glycoprotein expressed on the surface of most hematopoietic cells, has been implicated in cell adhesion and signaling. The reduced expression of this antigen in patients with Wiscott-Aldrich syndrome, in which progressive immunodeficiency is a major problem, raised the question whether abnormal expression of this molecule could affect the susceptibility to infections in patients with myelodysplastic syndromes (MDS). We studied the expression of this antigen on the monocytes of ten patients with chronic myelomonocytic leukemia (CMML) and compared the results with 67 patients suffering from other MDS syndromes and with 18 healthy individuals. We chose this series as it plays an important role in MDS patients where in most cases the neutrophils are defective. We also examined the following antigens as indicative of activation and adhesion of the monocytes in these patients: CD11b, CD18, CD35, CD38, CD44, CD69. We found decreased expression of CD43 on the monocytes of the RA, RAS, RAEB, and RAEB-t patients compared with the CMML and controls. The other activation molecules studied were found to be upregulated, suggesting the existence of activated monocytes in these patients. The increased levels of soluble vascular cell adhesion molecule in these patients suggest vascular endothelial activation in the absence of infection. Further experiments are needed to investigate the significance of CD43 downregulation in these patients, its role in cell adherence and tissue migration, and the correlation of the phenomenon to the increased susceptibility to infections observed in these patients.