ABSTRACT
Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.
ABSTRACT
Objective:To explore the prognosis and clinical risk factor of thymoma patients after resection.Methods:A retrospectively analysis of 154 cases of thymoma patients underwent thymoma resection in Beijing Tongren Hospital (Myasthenia Gravis & Thymoma Diagnosis and Treatment Center, Capital Medical University) from January 2005 to December 2015, and then the progress-free survival was calculated by Kaplan- Meier method, the differences between curves were analyzed by log- rank test. There were 74 males and 80 females; the median age was 52(22-77)years. 121 cases(78.6%)complicated with myashenia gravis. Thymoma cases were classfied into 5 cases A, 35 cases AB, 27 cases B1, 56 cases B2 and 31 cases B3 respectively. There were 80, 16, 45 and 13 patients with Masaoka-Koga type Ⅰ-Ⅳ, respectively. 122 cases were treated by thoracoscopic assisted operation, 32 cases were treated by median sternum. The risk factors about group of gender, age, thymoma-associated MG (Myasthenia Gravis), completeness of resection, histologic type and Masaoka-Koga stage were calculated by Cox regression analysis. Results:The overall 1-, 5- 10-year progress-free survival rate of 154 cases were 98.7%, 88.3%, and 78.7%, respectively. The adverse prognostic factors for progress-free survival were age, completeness of resection, WHO histologic classification and Masaoka-Koga stage at univariate analysis. The age, WHO histologic classification and Masaoka-Koga stage were the independent risk factors at multivariate analysis.Conclusion:For thymoma, we suggest early discovery and early treatment. For the thymoma patients who are available for surgical treatment, all the tumor, thymus and surrounding adipose tissue should be resected. For the thymoma patients whose tumors cannot excise completely, adjuvant radiotherapy can reduce the risk for tumor recurrence after resection. For patients with thymoma after surgery, MG treatment is particularly critical for prognosis.
ABSTRACT
As a thymoid-related autoimmune disease, thymectomy has become one of the effective treatments for MG. We review the surgical indications of MG in this artical.