[Analysis of CHIP-Related Mutation and Risk of Cardio-Cerebrovasculars Events in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential (CHIP) related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events (CCEs) in patients with myeloproliferative neoplasms (MPNs). METHODS: The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed. Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients. RESULTS: Fifty-five cases of MPN (75.3%) showed positive in CHIP-related genes. There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia (ET) and polycythemia vera (PV). CHIP-related gene mutations were mainly single gene mutations, with mutation rate from high to low as JAK2V617F (63.0%, 46/73), ASXL1 (16.4%, 12/73), TET2 (11.0%, 8/73), DNMT3A (9.6%, 7/73), SRSF2 (6.9%, 5/73), SF3B1 (4.1%, 3/73), TP53(1.4%, 1/73) and PPM1D (1.4%, 1/73). The mutation rate of CHIP-related genes in MPN patients >60 years old was significantly higher than that in the patients ≤60 years old ï¼»91.7%(33/36) vs 59.5%(22/37)ï¼½. CCEs occurred in 27 MPNs patients (37.0%, MPNs/CCEs), and 5 had recurrent CCEs, all of which were arterial events. Age (62.8±12.8 years vs 53.9±15.8 years, P =0.015), IL-1ß level (17.7±26.0 vs 4.3±8.6, P =0.012), IL-8 level (360.7±598.6 vs 108.3±317.0, P =0.045), the proportion of the patients with thrombosis history (29.6% vs 2.2%, P =0.020), and the detection rate of CHIP-related mutations (88.9% vs 67.4%, P =0.040) in the group with CCEs were higher than those in the group without CCEs. Multivariate Logistic regression analysis showed that age（OR =0.917， 95%CI ：0.843-0.999, P =0.047）, thrombosis history (OR =34.148， 95%CI ：2.392-487.535, P =0.009), any CHIP-related mutations(OR =16.065， 95%CI ：1.217-212.024， P =0.035), and elevated level of IL-1ß (OR =0.929， 95%CI ：0.870-0.992， P =0.027) were independent risk factors for MPNs/CCEs. CHIP-related gene mutations were not associated with CCEs in MPN patients, but DNMT3A (OR =88.717， 95%CI ：2.690-292.482， P =0.012) and ASXL1 (OR =7.941， 95%CI ：1.045-60.353， P =0.045) were independent risk factors for CCEs in PV. CONCLUSION: There is a higher mutation rate of CHIP-related genes in MPN patients, especially those over 60 years old. Older age, thrombosis history, CHIP-related mutations and IL-1ß elevated levels are independent risk factors for CCEs in MPN. DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients. CHIP-related gene mutations and inflammatory cytokine IL-1 ß elevated levels may be the novel risk factors for CCEs in MPN.

A gibberellin-deficient maize mutant exhibits altered plant height, stem strength and drought tolerance.

KEY MESSAGE: The reduction in endogenous gibberellin improved drought resistance, but decreased cellulose and lignin contents, which made the mutant prone to lodging. It is well known that gibberellin (GA) is a hormone that plays a vital role in plant growth and development. In recent years, a growing number of studies have found that gibberellin plays an important role in regulating the plant height, stem length, and stressed growth surfaces. In this study, a dwarf maize mutant was screened from an EMS-induced mutant library of maize B73. The mutated gene was identified as KS, which encodes an ent-kaurene synthase (KS) enzyme functioning in the early biosynthesis of GA. The mutant was named as ks3-1. A significant decrease in endogenous GA levels was verified in ks3-1. A significantly decreased stem strength of ks3-1, compared with that of wild-type B73, was found. Significant decreases in the cellulose and lignin contents, as well as the number of epidermal cell layers, were further characterized in ks3-1. The expression levels of genes responsible for cellulose and lignin biosynthesis were induced by exogenous GA treatment. Under drought stress conditions, the survival rate of ks3-1 was significantly higher than that of the wild-type B73. The survival rates of both wild-type B73 and ks3-1 decreased significantly after exogenous GA treatment. In conclusion, we summarized that a decreased level of GA in ks3-1 caused a decreased plant height, a decreased stem strength as a result of cell wall defects, and an increased drought tolerance. Our results shed light on the importance of GA and GA-defective mutants in the genetic improvement of maize and breeding maize varieties.

The genome evolution and domestication of tropical fruit mango.

BACKGROUND: Mango is one of the world's most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other genera. Many species in this family produce family-specific urushiols and related phenols, which can induce contact dermatitis. RESULTS: We generate a chromosome-scale genome assembly of mango, providing a reference genome for the Anacardiaceae family. Our results indicate the occurrence of a recent whole-genome duplication (WGD) event in mango. Duplicated genes preferentially retained include photosynthetic, photorespiration, and lipid metabolic genes that may have provided adaptive advantages to sharp historical decreases in atmospheric carbon dioxide and global temperatures. A notable example of an extended gene family is the chalcone synthase (CHS) family of genes, and particular genes in this family show universally higher expression in peels than in flesh, likely for the biosynthesis of urushiols and related phenols. Genome resequencing reveals two distinct groups of mango varieties, with commercial varieties clustered with India germplasms and demonstrating allelic admixture, and indigenous varieties from Southeast Asia in the second group. Landraces indigenous in China formed distinct clades, and some showed admixture in genomes. CONCLUSIONS: Analysis of chromosome-scale mango genome sequences reveals photosynthesis and lipid metabolism are preferentially retained after a recent WGD event, and expansion of CHS genes is likely associated with urushiol biosynthesis in mango. Genome resequencing clarifies two groups of mango varieties, discovers allelic admixture in commercial varieties, and shows distinct genetic background of landraces.

A rare vascular complication in a patient with essential thrombocythaemia: spontaneous abdominal aortic dissection.

A 27-year-old woman complained of waist and back pain. Abdominal computed tomography angiography showed abdominal aortic dissection, the blood count revealed a high platelet count of 1655 × 109 /L. Negative for JAK2V617F, CALR and MPL mutations (i.e. triple-negative), the patient was diagnosed as essential thrombocythaemia (ET) with abdominal aortic dissection and was treated with cytoreduction and antiplatelet drugs. Cases of abdominal aortic dissection in ET have not been previously reported. As such, we proposed a mechanism of abdominal aortic dissection caused by endothelial dysfunction and further emphasised appropriate management in ET with abdominal aortic dissection.

[Marginal zone lymphoma with monoclonal immunoglobulin: three cases report and literatures review].

OBJECTIVE: To investigate the clinical features and treatment in patients of marginal zone lymphoma (MZL)with monoclonal immunoglobulin (McIg). METHODS: The clinical data of MZL patients with McIg, including 3 cases diagnosed and treated in Beijing Anzhen Hospital from Jan 2007 to Dec 2014 were retrospectively studied, meanwhile 36 patients searched from literatures were reviewed. RESULTS: Of a total of 39 patients, the ratio of male and female was 1.05∶1 with an average age of 65.1± 12.3 years old. 28 cases (71.8%)were with mucosa associated lymphoid tissue lymphomas (MALTL), 9 cases (23.1% )with nodal marginal zone lymphoma, and 2 cases (5.1%)with splenic marginal zone lymphoma. Nine cases (23.1% )were in the early stage, 30 cases (76.9%)in the advanced stage. The common initial symptom was non-mass lesions (65.5%), such as skin purpura, peripheral neuropathy; 13 patients (33.3% )were accompanied by autoimmune phenomenon, and most were with Sjogren's syndrome. Among MALTL patients, the common primary lesion was in non- gastrointestinal tract (17 cases, 60.7%). Most of patients with McIg were one with McIgM (82.0%); the others with McIgA, Mcκ-light chain, McIgG and double McIg. The level of plasma McIgM was (25.55±21.31)g/L, which was higher in advanced stage patients than in early stage ones [(29.85±20.60)g/Lvs (3.23±2.95)g/L,P= 0.008]. The complete remission (CR)rate was 56.0% and the overall response rate (ORR)92.0%, respectively in 30 patients treated by chemotherapy. At a median follow- up of 10 months, the 3- year progression free survival and the 3-year overall survival were 44.7% and 76.5%, respectively. The rates of ORR and CR in the patients received rituximab- included regimen were seemly better than those without rituximab one (100.0%vs 78.6%, 63.6%vs 50.0%;P>0.05), but no statistic differences were found. The CR rate in patients with McIgM was significantly higher than that with non- McIgM (P=0.026). The plasma McIgM level decreased after chemotherapy (P=0.002). CONCLUSION: The MZL with McIg, perhaps a kind of unique subtype, usually occurred in 60 years or older patients. It was often diagnosed in patients of advanced stage and susceptible to autoimmune phenomenon. MALTL in non- gastrointestinal tract was more prone to find McIg. In MZL patients with McIg, McIgM was more common and other McIg rare. Rituximab-included regimen produced a better therapeutic response.