Oligonucleotide uptake in human hematopoietic cells is increased in leukemia and is related to cellular activation

The use of antisense oligonucleotides as tools for modulating gene expression represents a novel strategy for designing drugs to treat a variety of diseases. Several factors, including cellular uptake and internalization of the oligonucleotides, are important parameters in determining the effectiveness of antisense agents such as therapeutic drugs. We have studied oligonucleotides uptake in normal and leukemic human hematopoietic cells, such as peripheral blood, bone marrow (BM), and HL-60 cell line; and have found that, in normal human blood and BM, myeloid cells and B cells preferably took up more oligonucleotides than T cells. There was no marked difference in oligonucleotide uptake between CD4+ helper T cells and CD8+ cytolytic T cells. Leukemic cells had greater oligonucleotide uptake than their normal counterparts. Furthermore, oligonucleotide uptake was closely related to cell activation status and can be modulated by growth factors or inhibitors. These studies provide a basis for using oligonucleotides as therapeutic drugs both in vitro and in vivo.     

A useful relationship between the presence of extramedullary erythropoeisis and the level of the soluble form of the transferrin receptor in a large cohort of adult patients with thalassemia intermedia: a prospective study

In thalassemia intermedia (TI), the increase in bone marrow hemopoietic activity frequently leads to extramedullary erythropoeisis (EMH), but its relationship with the soluble form of transferrin receptor (sTfR) which fully reflects the marrow erythropoietic activity, has not yet been explored. From January 2007 to December 2010, all TI patients attending at our center were prospectively enrolled to undergo sTfR assay and MRI or CT (if claustrophobic) scan evaluation for the presence of paraspinal EMH. A total of 59 patients with TI were studied; EMH involved 23 (39%) patients; overall, the concentration of sTfR varied from 2.6 to 20.6 (mean = 8.7) mg/L, but in splenectomized group and in unsplenectomized group, it varied from 4.2 to 17.8 (mean ± SD = 9.86 ± 3.33) mg/L and from 2.6 to 20.6 (mean ± SD = 7.25 ± 3.9) mg/L, respectively with a statistically significant intergroup difference (p < 0.01). The cutoff point at 8.6 mg/L using the ROC curve showed a sensitivity of 78.3% and a specificity of 72.2%, in predicting EMH but, in unsplenectomized subgroup, they raised to 100% and 90.9%, respectively. These data showed that in TI the level of sTfR could represent a predictive factor of EMH particularly in patients with spleen.     

Splenectomy is a risk factor for developing hyperuricemia and nephrolithiasis in patients with thalassemia intermedia: A retrospective study

Few data are available on the prevalence and the risk factors for the presence of kidney stones and hyperuricemia in patients with thalassemia intermedia. We retrospectively reviewed the charts and radiological studies of 89 patients with thalassemia intermedia followed at our clinic with routine biochemical examination and radiological imaging of the urinary tract. Renal calculi were identified in 11 patients (12%) and 22 patients (25%) were under uricosuric treatment for hyperucemia. The prevalence of nephrolithiasis increased with age but not in a statistically significant manner. Major risk factors for renal stone formation were splenectomy (in 91% of the cases) and higher number of erythroblasts. Patients with renal stones had higher mean creatinine level and lower GFR value with respect to those observed in patients not affected. Our data suggest that splenectomy, by further increasing erythrocyte turnover and number, may be directly involved in the pathogenesis of hyperuricemia and nephrolithiasis observed in thalassemia intermedia patients.