[Establishment and validation of prognosis predictive model using m6A RNA methylation regulators in children acute myeloid leukemia].

Objective: To figure out the association between the expression of m6A RNA methylation regulators and the prognosis of children AML, and provide genetic markers for monitoring the progression and recurrence of AML. Methods: Twenty two m6A RNA methylation regulators were firstly analyzed using the data from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) database and The Genotype-Tissue Expression(GTEx) database, Wilcoxon rank test was performed to analyze the differentially expression of m6A RNA methylation regulators between the AML and normal tissue, 296 AML children were divided into training cohort and validation cohort by simple random sampling method, Lasso regression was used to screen out the risk factors and the multivariate Cox regression was applied for establishing prognosis predicting model in training cohort. Kaplan-Meier survival curve, time-dependent ROC curve and multivariate Cox regression were used to estimate the efficiency of risk score calculated by predictive model in validation cohort. Results: Twenty one m6A genes were up regulated in AML compared to Normal patients. Five m6A RNA methylation regulators(ZC3H13, YTHDC2, HNRNPA2B1, METTL3, METTL5) were included in final predicting model. Risk score could independently predict the survival of AML patients in training cohort(HR:2.72, 95%CI: 1.54-4.81, P=0.000 6) and validation cohort(HR:2.01, 95%CI:1.14-3.50, P=0.016). Low-risk patients had better prognoses than high-risk patients both in training cohort(P=0.001 9) and validation cohort(P=0.023). Conclusion: This prognosis predicting model constructed by m6A RNA methylation regulators could independently predict the survival prognosis in AML children, and should be helpful for clinical therapy.

Current status of thalassemia in minority populations in Guangxi, China.

Thalassemia is one of the most common monogenic disorders in the world. In order to develop a community-based prevention program, we screened 12,900 individuals for alpha- and beta-thalassemia in Baise City, Guangxi, China, with hematological methods and molecular assays. We found that the frequency of carriers in this area for alpha-thalassemia is 15%. Beta-thalassemia carriers comprise 4.8% of the populations. Five mutations account for 98% of alpha-thalassemia [--SEA 46.7%; -alpha/4.2, 23.9%; -alpha/3.7, 21.7%; hemoglobin (Hb) Constant Spring, 6.5%; Hb Quong Sze, 1.1%]. Seven mutations in the beta-globin gene account for 99% of the mutations [codon (CD) 41/42 (-TCTT) (39.4%), CD 17(A-->T) (32%), CD 71/72 (+A) (7.4%), -28 (A-->G) (5.8%), IVS-2-654 (C-->T) (5.8%), CD26 (Hb E) (4%), IVS-1 (G-->A) (3.7%), and CD 43(G-->T) (1.9%)]. Most individuals with alpha-thalassemia major die in the uterus or shortly after birth. Among 106 patients with beta-thalassemia major followed by our clinic, the majority died before 5 years of age. Knowledge surveys about thalassemia were conducted. Our results show a severe lack of knowledge about thalassemia in both medical professionals and in the general populations. This study shows that thalassemia is a very severe public health issue in minority populations in Baise City, China. Identification of the common mutations will allow us to design cost-effective molecular tests. There is an urgent need to educate the general population and the medical community for a successful community-based prevention program.

Hb Wuming or alpha 2 11(A9)Lys substituting for Gln beta 2.

A fast-moving hemoglobin variant was found in five members of a Chinese family of the Wuming district. The relative amount of this alpha chain variant in the heterozygote was about 20%. The abnormality caused no ill effects in its carriers. Sequence analysis identified a Lys substituting for Gln substitution at position alpha-11 (A9).

Studies of beta-thalassemia mutations in families living in three provinces in southern China.

beta-Thalassemia is a common disease in Southern China and 10 different mutations or frameshifts are responsible for most types of beta-thalassemia in this area. We studied 126 chromosomes of 80 beta-thalassemia patients from the Guangxi, Guangdong, and Sichuan Provinces using the polymerase chain reaction followed by dot-blot hybridization with specific oligonucleotide probes. The most common mutation in the three provinces is the frameshift at codons 41-42, followed by the A----T mutation at codon 17. The A----G mutation at nt -29 of the promoter is common in Sichuan but not in the other two provinces. Three mutations (T----C at nt -30; G----T at IVS-I-1, and G----C at IVS-I-5) were not observed. These data were used to initiate a prenatal diagnosis program using the same techniques for identification. Eleven fetuses at risk for beta-thalassemia have been diagnosed.