The Polycomb BMI1 Protein Is Co-expressed With CD26+ in Leukemic Stem Cells of Chronic Myeloid Leukemia

The Polycomb gene BMI1 expression exerts a negative predictive impact on several hematological malignancies, such as acute and chronic myeloid leukemia (CML), myelofibrosis, and follicular lymphoma. As already demonstrated in CML, BMI1 is responsible for the resistance to the tyrosine kinase inhibitors (TKIs) in a BCR-ABL1-independent way. Even if, it is unknown where BMI1 in CML is expressed (in progenitors or more mature cells). We decided, therefore, to evaluate if and where the BMI1 protein is located, focusing mainly on the CD34+/CD38-/CD26+ CML progenitors. To begin we measured, by flow cytometry, the proportion of CD34+/CD26+ cells in 31 bone marrow samples from 20 CML patients, at diagnosis and during treatment with imatinib. After that the bone marrow blood smears were stained with antibodies anti-CD26, BCR-ABL1, and BMI1. These smears were observed by a confocal laser microscope and a 3D reconstruction was then performed. At diagnosis, CD34+/CD26+ cells median value/μL was 0.48; this number increased from diagnosis to the third month of therapy and then reduced during treatment with imatinib. The number and behavior of the CD26+ progenitors were independent from the BCR-ABL1 expression, but they summed up what previously observed about the BMI1 expression modulation. In this work we demonstrate for the first time that in CML the BMI1 protein is co-expressed with BCR-ABL1 only in the cytoplasm of the CD26+ precursors; on the contrary, in other hematological malignancies where BMI1 is commonly expressed (follicular lymphoma, essential thrombocytemia, acute myeloid leukemia), it was not co-localized with CD26 or, obviously, with BCR-ABL1. Once translated into the clinical context, if BMI1 is a marker of stemness, our results would suggest the combination of the BMI1 inhibitors with TKIs as an interesting object of research, and, probably, as a promising way to overcome resistance in CML patients

Esophageal papilloma: Flexible endoscopic ablation by radiofrequency

Squamous papilloma of the esophagus is a rare benign lesion of the esophagus. Radiofrequency ablation is an established endoscopic technique for the eradication of Barrett esophagus. No cases of endoscopic ablation of esophageal papilloma by radiofrequency ablation (RFA) have been reported. We report a case of esophageal papilloma successfully treated with a single session of radiofrequency ablation. Endoscopic ablation of the lesion was achieved by radiofrequency using a new catheter inserted through the working channel of endoscope. The esophageal ablated tissue was removed by a specifically designed cup. Complete ablation was confirmed at 3 mo by endoscopy with biopsies. This case supports feasibility and safety of as a new potential indication for Barrx(TM) RFA in patients with esophageal papilloma

Remission of type 2 diabetes in patients undergoing biliointestinal bypass for morbid obesity: A new surgical treatment

Background Nutrient interaction with the mid-gut may play a role in improving type 2 diabetes mellitus (T2D) after bariatric surgery. However, Roux-en-Y gastric bypass, biliopancreatic diversion, and sleeve gastrectomy include diversion of food from the duodenum and/or partial gastrectomy. Biliointestinal bypass (BIBP) was introduced to eliminate the major side effects of jejunoileal bypass. It does not involve any change to the anatomy of the stomach or the duodenum. A prospective evaluation of the role of BIBP in glycemic control has not been reported. Objectives Longitudinal evaluation of T2D after BIBP. Setting University hospitals in Europe and Canada. Method The effects of BIBP on metabolism and glycemia in 28 consecutive patients with T2D were evaluated over 2 years. Results Decreases (P<.001) in fasting glycemia, insulinemia, and homeostasis model assessment were observed 3 months after surgery, were improved after 1 year, and remained stable after 2 years. Glycosylated hemoglobin levels decreased at 3, 12, and 24 months after surgery (from 9.2±2.1 to 6.3±1.1 (P<.0001), 4.9±1.7 (P<.0001), and 4.8±1.1 (P<.0001), after 3, 12, and 24 months, respectively). Medical therapy was discontinued in 83% (20 of 24) of the patients; for the remaining 17% (4 of 24), therapy was reduced to oral hypoglycemic agents. Conclusion BIBP had a favorable risk-benefit relationship and positive metabolic effects in the short term. How BIBP achieves optimal glycemic control and whether it improves β-cell function and/or insulin sensitivity require further study