The Ten Eleven Translocation 1 (TET1) gene encodes an epigenetic modifying molecule that is involved in demethylation of 5-methylcytosine. In hematological malignancies, loss-of-function mutations of TET2, which is one of the TET family genes including TET1, are frequently found, while the mutations of TET1 are not. However, clinical studies have revealed that TET1 is highly expressed in some cases of the hematological malignancies including acute myeloid leukemia. Indeed, studies by mouse models using conventional Tet1 knockout mice demonstrated that Tet1 is involved in myeloid leukemogenesis by Mixed Lineage Leukemia (MLL) fusion gene or TET2 mutant. Meanwhile, the other study showed that Tet1 is highly expressed in hematopoietic stem cells (HSCs), and that deletion of Tet1 in HSCs enhances potential self-renewal capacity, which is potentially associated with myeloid leukemogenesis. To examine the role of Tet1 in myeloid leukemogenesis more precisely, we generated novel conditional Tet1-knockout mice, which were used to generate the compound mutant mice by crossing with the inducible MLL-ENL transgenic mice that we developed previously. The leukemic immortalization in vitro was not critically affected by conditional ablation of Tet1 in HSCs with the induced expression of MLL-ENL or in hematopoietic progenitor cells retrovirally transduced with MLL-ENL. In addition, the leukemic phenotypes caused by the induced expression of MLL-ENL in vivo was not also critically affected in the compound mutant mouse model by conditional ablation of Tet1, although we found that the expression of Evi1, which is one of critical target genes of MLL fusion gene, in tumor cells was remarkably low under Tet1-ablated condition. These results revealed that Tet1 was dispensable for the myeloid leukemogenesis by MLL-ENL, suggesting that the therapeutic application of Tet1 inhibition may need careful assessment.

Objective The safety and prognosis of complete stone removal for the treatment of choledocholithiasis in older patients are unknown. This multicenter retrospective study assessed the outcomes of complete stone removal in elderly patients (! 90 years) with respect to the prognosis. Methods We divided patients who underwent endoscopic cholangiopancreatography for choledocholithiasis into two groups: complete stone removal or incomplete stone removal with plastic stent insertion. The patient characteristics, adverse events, number of endoscopic cholangiopancreatographies, overall survival rates, and disease-specific cumulative death were compared between the groups. Patients Two hundred and twenty-three participants ! 90 years old were included in the study, including 48 (22%) men and 175 (78%) women. The median age was 92 (range, 90-104) years old. There were 160 (72%) and 63 (28%) patients in the complete and incomplete groups, respectively. Results: The age, performance status, comorbidities, severe complication rates, and stone diameter were comparable between the groups. The proportion of patients with at least 5 stones was significantly higher in the incomplete group than in the complete group (complete group: 8.1% [13/160] and incomplete group: 21% [13/63], p<0.01). The overall survival rate was significantly higher in the complete group (p<0.01), while the disease-specific cumulative death rate was higher in the incomplete group (p<0.01). Conclusion Complete stone removal for choledocholithiasis may contribute to a better prognosis in elderly patients ! 90 years old.

A 64-year-old man with a history of diabetes and gallstones was admitted to our institution with suspected pancreatic malignancy. Computed tomography (CT) revealed multiple pancreatic cysts and massive ascites, and endoscopic ultrasonography (EUS) revealed a 28×27-mm hypoechoic mass in the pancreatic head. An EUS-guided fine-needle aspiration biopsy was performed, and there were no malignant findings. Based on the test results and imaging findings, type 1 autoimmune pancreatitis was suspected. The patient was administered 30 mg of prednisolone daily. After 11 days, CT revealed that the pancreatic cysts and ascites had reduced in size.