The precise genetic events leading to myelodysplastic syndromes (MDSs) and leukemic transformation remain poorly defined. Even less is known about adult familial MDS. We report an adult MDS family in whom enriched tissue-specific transcripts were derived by subtractive hybridization of cDNA from the mononuclear and CD34 þ cells of affected and unaffected family members. These expression libraries were then hybridized to Genome Discovery arrays containing 18 404 genes and expressed sequence tags, and several clusters of differentially expressed genes were identified. A group of 21 genes was underexpressed (45-fold) in affected vs unaffected family members, and among these were transcription factors and genes involved in myeloid differentiation, such as ZNF140 and myeloid nuclear differentiation antigen (MNDA). Another group of 36 genes was overexpressed (45-fold), and these encoded proteins belonging to signaling pathways, such as Ras-and Fos-related genes. The top two genes downregulated in this MDS family, ZNF140 and MNDA, were similarly altered in another MDS family, and in some cases of sporadic MDS. Our data suggest that we have identified genes differentially expressed in adult familial MDS, and that alteration of some of these genes may also be important for the evolution of different stages or severity of sporadic MDS.

clinical evaluation of the antiprothrombin assay and the antiphosphatidylserine ⁄ prothrombin assay, and comparison with other antiphospholipid antibody assays. Mod Rheumatol 2006; 16:158-64. 5 Cervera R, Piette JC, Font J et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46:1019-27. 6 Uthman IW, Khamashta MA. Livedo racemosa: a striking dermatological sign for the antiphospholipid syndrome. J Rheumatol 2006; 33:2379-82. 7 Emmerich J, Rosendaal FR, Cattaneo M et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism -pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 2001; 86:809-16. 8 Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med 2004; 350:1862-71. 9 Miller DJ, Maisch SA, Perez MD et al. Fatal myocardial infarction in an 8-year-old girl with systemic lupus erythematosus, Raynaud's phenomenon, and secondary antiphospholipid antibody syndrome.

Resistance to cytotoxic agents is a common clinical problem in the treatment of chronic lymphatic leukaemia (CLL). The multidrug resistant (MDR) phenotype characterized by increased levels of a specific cell membrane p-glycoprotein, confers cross resistance to a wide range of structurally dissimilar antineoplastic drugs. We have studied the expression of this p-glycoprotein in chronic lymphatic leukaemia measured by immunofluorescence using a monoclonal antibody MRK 16 by flow cytometry. Initial results showed that only 12% of lymphocyte samples from CLL patients showed increased p-glycoprotein, conflicting with a previous observation that 53% of CLL patients had an increased level of mdr-1 mRNA. Treatment of the cells with neuraminidase to remove sialic acid residues increased the proportion of patients showing increased p-glycoprotein to 52%. This suggest that in a subset of CLL patients post translational modification of the protein occurs masking the epitope recognized by MRK 16. Abnormal sialylation patterns associated with malignancy are a well-recognized phenomenon.

The metabolic consequences of thiazide diuretics are well known. The elderly to whom these agents are widely prescribed may be particularly susceptible. To quantify this metabolic risk, plasma and intracellular electrolytes and plasma glucose were measured in the elderly population of a Somerset village. Highly significant reductions in both plasma and cellular magnesium and potassium were found in the 47 thiazide-treated people. Forty-eight per cent of the thiazide-treated group were hypomagnesaemic and 28% were hypokalaemic. Thus, magnesium and potassium depletion are commonly associated with thiazide therapy in the elderly. These metabolic effects should be considered carefully prior to the use of these agents.