Differential expression of BCL-2 oncoprotein and Fas antigen on normal peripheral blood and leukemic bone marrow cells. A flow cytometric analysis.

BACKGROUND: Fas antigen (Ag) has recently been identified as the putative surface molecule capable of transducing apoptotic signals into cells. Alterations in the expression of proto-oncogene bcl-2 have been implicated in the regulation of apoptosis. MATERIALS AND METHODS: By employing a monoclonal antibody to bcl-2 protein (124 clone) and to Fas Ag (UB2 clone) the expression of these molecules was analyzed at flow cytometry on bone marrow (BM) and peripheral blood (PB) samples from patients suffering from different lymphoid and myeloid leukemic diseases (27 acute non-lymphocytic leukemia [ANLL]; 14 acute lymphocytic leukemia [ALL]; 19 B-cell chronic lymphocytic leukemia [CLL]; 2 Ph1+ chronic myeloid leukemia [CML]; one CD8+ T-cell chronic lymphoproliferative disorders). Results were compared with those observed on normal PB leukocytes and BM B-cell precursors from patients with non-neoplastic hematological disorders. RESULTS: Fas Ag was constitutively expressed by both monocytes and neutrophils, while lymphocytes expressed bcl-2 with no difference between B and T cell subsets. Interestingly, bcl-2 expression was always absent on neutrophils. When dealing with ANLL patients, a relatively low bcl-2 and high Fas Ag phenotype characterized subtypes with granulocytic (M2) or promyelocytic (M3) differentiation. This observation was confirmed in a small number of patients for whom bcl-2 levels were quantified as antibody binding capacity (ABC) in molecules/cell. Leukemic cells from patients with ALL constitutively expressed bcl-2, the pattern of this expression being quantitatively lower than that of immature B-cell precursors. Finally, high bcl-2 and low Fas Ag expression represented a crucial part of the B-cell CLL immunophenotype. CONCLUSIONS: Although based on a small number of patient and control samples, our results suggest that bcl-2 and Fas Ag are coordinately expressed on normal PB leukocytes. Fas Ag is expressed at low levels on B-CLL cells, generally considered long-surviving cells. The relatively lower bcl-2-expression detected in both M2 and M3 subtypes may explain, at least in part, the higher remission rates obtained in these forms of ANLL than in other less differentiated morphological variants.

Spectrum of beta-thalassemia mutations in Calabria: implications for prenatal diagnosis.

Using a combination of oligonucleotide probes and restriction endonuclease enzymes, we characterize beta-thalassemic mutations in 91 homozygous patients and 86 unrelated carriers. Overall, 268 beta-thalassemic genes were obtained. Eleven beta-globin mutations were identified, confirming the wide molecular heterogeneity of beta-thalassemia in Calabria. Information from the present study represents the mainstay for the development of a program of early prenatal diagnosis by direct detection of mutations in Calabria.

Hypothyroidism in patients with thalassemia syndromes.

Sixty transfusion-dependent thalassemic patients were studied by simultaneous measurement of circulating thyroid hormones, basal thyroid-stimulating hormone (TSH) and TSH response to thyrotropin-releasing hormone with the aim of evaluating the frequency of hypothyroidism in such patients, and the relationship between hypothyroidism and compliance with treatment and iron overload. Thyroid failure was present in 31 of the 60 patients. A correlation was found between impairment of thyroid functions, duration of chronic hypoxia and the activities of various transaminases. The results of this study emphasize the importance of early evaluation of thyroid function in thalassemic patients and suggest that anemia and hypoxia may potentiate the toxicity of iron deposition in endocrine glands.

Recurrent life-threatening epistaxis in a child with Bernard-Soulier syndrome controlled by bilateral ligation of external carotids and ethmoidal arteries.

Bilateral ligation of external carotids and ethmoidal arteries proved successful in controlling severe recurring epistaxis in a 13-year-old patient with Bernard-Soulier syndrome. In this child, epistaxis was the major bleeding symptom. Despite massive substitutive therapy, the patient suffered several life-threatening episodes of hypovolaemic shock. Although epistaxis is not reported as a cause of death in patients with haemostasis defect, our case might suggest that in selected cases with inherited platelet defect and intractable epistaxis so severe as to make normal or near-normal life impossible, surgical treatment could be considered.