Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs). We examined the individual and cooperative effects of these mutations on MPN development. Recipients of ...JAK2V617F cells developed primary myelofibrosis–like features; the addition of loss of TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoiesis, and modestly shorter survival. Double-mutant (JAK2V617F plus loss of TET2) myeloid cells were more likely to be in a proliferative state than JAK2V617F single-mutant myeloid cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the second recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and loss of TET2 developed and maintained MPNs in the second recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. In-vitro sequential colony formation assays also supported the observation that JAK2V617F did not maintain HSC functioning over the long-term, but concurrent loss of TET2 mutation restored it. Transcriptional profiling revealed that loss of TET2 affected the expression of many HSC signature genes. We conclude that loss of TET2 has two different roles in MPNs: disease accelerator and disease initiator and sustainer in combination with JAK2V617F.
•Loss of TET2 accelerates the degree of malignancy of MPNs in combination with JAK2V617F.•Loss of TET2 sustains MPNs in combination with JAK2V617F.
TET2 mutation in diffuse large B-cell lymphoma Kubuki, Yoko; Yamaji, Takumi; Hidaka, Tomonori ...
Journal of Clinical and Experimental Hematopathology,
2017, Letnik:
56, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Ten-eleven translocation-2 (TET2) mutation is frequently observed in myeloid malignancies, and loss-of-function of TET2 is essential for the initiation of malignant hematopoiesis. TET2 mutation ...presents across disease entities and was reported in lymphoid malignancies. We investigated TET2 mutations in 27 diffuse large B-cell lymphoma (DLBCL) patients and found a frameshift mutation in 1 case (3.7%). TET2 mutation occurred in some populations of DLBCL patients and was likely involved in the pathogenesis of their malignancies.
The patient was a 63-year-old man. He was examined by a local doctor for dyspnea, where he was administered oral steroids and started on inhalation therapy for a diagnosis of bronchial asthma. ...However, his symptoms worsened and he was brought to our hospital. On admission, he was diagnosed with atrial fibrillation and acute heart failure. Upon administration of anticoagulants to prevent embolism in this patient with atrial fibrillation, the patient developed bloody stool. Colonoscopy revealed multiple diverticula in the hepatic flexure, along with ulcers and white coating localized to that area. Diverticular colitis was initially suspected, but vegetative amoebas were found in a tissue biopsy of the ulcers and he was diagnosed with amebic colitis. The ulcers healed with administration of metronidazole. We report this case in which amebic colitis developed in a man with asymptomatic Entamoeba histolytica infection from the use of steroids and anticoagulants, with the lesions localized in the area with multiple colon diverticula.
TET2 Mutation in Adult T-Cell Leukemia/Lymphoma Shimoda, Kazuya; Shide, Kotaro; Kameda, Takuro ...
Journal of Clinical and Experimental Hematopathology,
2015, Letnik:
55, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Loss-of-function of ten-eleven translocation-2 (TET2) is a common event in myeloid malignancies, and plays pleiotropic roles, including augmenting stem cell self-renewal and skewing hematopoietic ...cells to the myeloid lineage. TET2 mutation has also been reported in lymphoid malignancies; 5.7～12% of diffuse large B-cell lymphomas and 18～83% of angioimmunoblastic T-cell lymphomas had TET2 mutations. We investigated TET2 mutations in 22 adult T-cell leukemia/lymphoma (ATLL) patients and identified a missense mutation in 3 cases (14%). TET2 mutation occurred in a number of ATLL patients and was likely involved in their leukemogenesis. J Clin Exp Hematop 55(3) : 145-149, 2015
Dear Editor, Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) that primarily involves the megakaryocytic lineage, and is characterized by increased numbers of large, mature ...megakaryocytes in bone marrow as well as sustained thrombocytosis. Mutations in JAK2 or calreticulin (CALR) are present in about 50% and 25% of patients with ET, respectively, and these mutations are thought to drive MPN 1. CALR and JAK2 mutations are mutually exclusive in MPNs 1. Compared with patients with JAK2-mutated ET, patients with CALR-mutated ET have lower Hb levels and lower numbers of granulocytes, but higher numbers of platelets 2-6. The CALR-mutated patients also have a lower incidence of thrombosis during their clinical course. Genetic background such as race may influence the risk of thrombosis, and recent study reported that Japanese ET patients with JAK2 mutation had a higher cumulative incidence of thrombosis than those with CALR mutations, although the differences were not significant 6. Therefore, we analyzed the impact of JAK2 and CALR mutations on clinical features and thrombotic events in Japanese patients with ET. KCI Citation Count: 0
Background and Aim. It is difficult to master the skill of discriminating gastric adenoma from early gastric cancer by conventional endoscopy or magnifying endoscopy combined with narrow-band ...imaging, because the colors and morphologies of these neoplasms are occasionally similar. We focused on the surrounding gastric mucosa findings in order to determine how to discriminate between early gastric cancer and gastric adenoma by analyzing the characteristics of the gastric background mucosa. Methods. We retrospectively examined 146 patients who underwent endoscopic submucosal dissection for gastric neoplasm between October 2009 and January 2015. The boundary of atrophic gastritis was classified endoscopically according to the Kimura-Takemoto classification system. Of 146 lesions, 63 early gastric cancers and 21 gastric adenomas were ultimately evaluated and assessed. Results. Almost all gastric adenomas were accompanied by open-type gastritis, whereas 47 and 16 early gastric cancers were accompanied by open-type and closed-type gastritis, respectively (p = 0.037). Conclusions. The evaluation of the boundary of atrophic gastritis associated with gastric neoplasms appears to be useful for discrimination between early gastric cancer and gastric adenoma. When gastric neoplasm is present in the context of surrounding localized gastric atrophy, gastric cancer is probable but not certain.
TET2 Mutation in Adult T-Cell Leukemia/Lymphoma Kazuya Shimoda; Kotaro Shide; Takuro Kameda ...
Journal of Clinical and Experimental Hematopathology,
12/2015, Letnik:
55, Številka:
3
Journal Article
Recenzirano
Loss-of-function of ten-eleven translocation-2 (TET2) is a common event in myeloid malignancies, and plays pleiotropic roles, including augmenting stem cell self-renewal and skewing hematopoietic ...cells to the myeloid lineage. TET2 mutation has also been reported in lymphoid malignancies; 5.7-12% of diffuse large B-cell lymphomas and 18-83% of angioimmunoblastic T-cell lymphomas had TET2 mutations. We investigated TET2 mutations in 22 adult T-cell leukemia/lymphoma (ATLL) patients and identified a missense mutation in 3 cases (14%). TET2 mutation occurred in a number of ATLL patients and was likely involved in their leukemogenesis.
Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease. Cyanotic spells occur more frequently after infancy in unrepaired cases. Acute esophageal necrosis (AEN) is a rare ...disease that causes circumferential mucosal necrosis in the distal esophagus. We report the case of a 26-year-old man who was admitted due to coffee-ground emesis, black stools, and decreased oxygen saturations. The patient had an unrepaired ToF and a congenital portosystemic venous shunt. An upper gastrointestinal endoscopy revealed AEN, which could be due to unstable hemodynamics of cyanotic spells. This is the first adult case presenting these 2 conditions occurring simultaneously.
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