Tcl1 protein functions as an inhibitor of de novo DNA methylation in B-cell chronic lymphocytic leukemia (CLL).

B-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene (TCL1) in mouse B cells causes a CD5(+) leukemia similar to aggressive human CLL. To examine the mechanisms by which Tcl1 protein exerts its oncogenic activity in B cells, we performed proteomics experiments to identify its interacting partners. We found that Tcl1 physically interacts with de novo DNA methylthansferases Dnmt3A and Dnmt3B. We further investigated the effects of Tcl1 up-regulation on the enzymatic activity of Dnmt3A and found that Tcl1 overexpression drastically inhibits Dnmt3A function. In addition, B cells from TCL1 transgenic mice showed a significant decrease in DNA methylation compared with WT controls. Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis.

Pólipo fibroepitelial benigno de ureter distal / Benign distal ureteral fibroepithelial polyp

The authors present a rare case of benign fibroepithelial polyp at distal ureter. A nineteen-year-old man with macroscopic hematuria and no lumbar pain during the last three months presented to the urological clinic. The ultrasonography showed a polypoid lesion at the distal third of the left ureter, causing intermittent urinary obstruction at vesicoureteral junction. The intravenous pyelography showed a mobile filling defect following the ureteral peristalsis. The cistoscopy revealed a red polyp protruding through the ureteral meatus. The urinary cytology and biopsy are negative for malignancy. At surgery, a 10 cm polypoid lesion with a large pedicle (causing ureteral intussusseption) was noted 1.5 cm above the iliac vessels and passing through the left ureteral meatus. The patient was submitted to a left distal ureterectomy, with bladder cuff resection, ureteroneocistostomy with a Politano-Leadbetter technique and psoas hitch. The pathologic examination showed a benign fibroepithelial ureteral polyp. The patient was discharged on the sixth postoperative day, This is an interesting case due to the rare topography affected (commonly occurring at renal pelvis or superior ureter). The endoscopic resection of the lesion was not indicated due to the impossibility to achieve complete resection because of its large pedicle. In similar cases, a previous endoscopic biopsy is recommended to avoid an unnecessary nephroureterectomy, which is performed in up to 35 percent of the cases reported in literature