Intracellular pH regulation of SV-40 virus transformed human MRC-5 fibroblasts and cell membrane cholesterol

Alterations in membrane cholesterol could affect the activity of various membrane transporters, including the Na(+)-H+ antiport. The effect of cellular cholesterol depletion (with phosphatidylcholine liposomes) and enrichment (with cholesterol and phosphatidylcholine liposomes) on cellular pH regulation was studied in SV-40 virus transformed human MRC-5 fibroblasts. Cellular cholesterol depletion led to activation of the Na(+)-H+ antiport by an increased maximal velocity (Vmax) of the transporter, with no changes in the apparent dissociation constant (Kd) or Hill coefficient for intracellular H+. Cholesterol enrichment had no effect on the activation of the Na(+)-H+ antiport by intracellular acidosis. However, activation of the Na(+)-H+ antiport by an osmotic stimulus was enhanced in cholesterol-depleted cells and reduced in cholesterol-enriched cells. Liposomes that had no effect on cellular cholesterol did not alter the activation of Na(+)-H+ antiport activity by intracellular acidosis or an osmotic stimulus. Thus in situ modification of cellular cholesterol altered Na(+)-H+ antiport activity differently depending on the type of activating stimulus.

Congenital hypoplastic anemia (Diamond-Blackfan syndrome) terminating in acute myelogenous leukemia

A 31-yr-old female with congenital hypoplastic anemia (Diamond-Blackfan syndrome) whose long course terminated in acute myelogenous leukemia is described. In contrast to Fanconi anemia, malignant transformation rarely occurs in congenital hypoplastic anemia. This patient's diagnosis of congenital hypoplastic anemia is supported by her clinical course, absence of renal abnormalities, a negative family history for hematologic disorders, normal chromosome studies, failure of her skin fibroblasts to transform in culture with SV-40 virus, macrocytic erythrocyte indices, erythrocyte enzyme studies, and bone marrow findings. Only two other cases of malignancy have been reported in patients with congenital hypoplastic anemia. The development of malignancy in these patients suggests that malignant transformation may be a concern in the long-term progression of congenital hypoplastic anemia.