MDS-associated Oncogene And Aplastic Anemia

Background:Aplastic anemia (AA) is much more common in China compared to that in western countries, which represents a medical challenge for patients, physicians and the health authorities. Certain somatic genes mutations were shown in various myeloid malignancies and correlated with clinical and laboratory features. Evolution of AA to myelodysplastic syndromes (MDS) was a serious long-term clonal complication, we postulated that somatic mutations were present in a subset of AA, which predicted prognosis and clonal evolution.Methods:In this study, we analyzed mutations in ASXL1, TET2, RUNX1, TP53, K-RAS and N-RAS in 138 Chinese patients with AA.Results:Somatic mutations in AA were detected in 24 patients (17.4%), including ASXLI mutations in 14 patients (10.1%), TET2 in 10 patients (7.3%), no mutations were detected in RUNX1, TP53, K-RAS and N-RAS. AA patients with and without ASXL1 mutations showed similar initial clinical and biological parameters, but patients with ASXL1 mutations had a greater risk of transformation to MDS compared to the counterpart patients (P=0.014). TET2 mutations which occurred more frequently in patients received antithymocyte globulin (ATG) (P=0.008) were closely associated with a good response to ATG (P=0.013), but had no relationship with evolution to MDS (P=0.543).Conclusions:Thus, our results identified that somatic mutations which were common in myeloid malignancies also existed in AA; Moreover, patients with different mutations showed distinct clinical and biological features.Background:ASXL1 mutations have been reported in various myeloid malignancies and are independently associated with an adverse outcome, but no attention was paid to its polymorphism. Aplastic anemia (AA) is considered a "benign" disease, our previous study showed that ASXL1 mutations were also common in patients with AA and associated with progression to myelodysplastic syndromes (MDS), we postulated that some ASXL1 single nucleotide polymorphisms (SNPs) may also relevant to AA.Methods and Findings:In this study, we analyzed ASXL1 SNPs and biological features in 134 Han Chinese patients with AA, five SNPs were identified,8.2%(11 of 134) patients unexpectedly had the recurrent conjoined rs62206933, rs117901891 and rs74638057 genotype (WT1), compared to 0%(0 of 64) controls (P=0.043), in addition, none of rs62206933, rs117901891 and rs74638057 genotype occurred separately in any patients with AA. The WT1 genotype was more frequent in less than 16 years old and more than 50 years old patients, compared to 16-50 years old patients (P=0.016), and had higher serous TNF (P=0.024), other pretreatment clinical and biological parameters had no significant difference. The WT1 genotype was closely associated with a bad prognosis in patients with non-severe AA (P=0.025). Patients with WT1 had a greater risk of transformation to MDS than the counterpart patients (P=0.001).Conclusions:Thus, our results showed that some myeloid malignancy-related gene was also associated with "benign" AA, patients with WT1 genotype showed distinct clinical and biological features.Objective To explore the value of genetic detection and changes of red cell enzyme activities in a-thalassaemia.Methods Three a-thalassaemia patients were further processed to detection of the gene of thalassaemia by PCR-trans-dot blot and gap-PCR, and analyses of red cell enzymes activities, including pyruvatekinase (PK), pyrimidine 5’nucleotidase (P5’N) and glucose-6-phosphate dehydrogenase (G-6-PD).Results Red cells in 3 a-thalassaemia cases were microcytic hypochromic with obvious augmented target and basophilic stippling erythrocytes.2 patients had anemia, splenomegaly, hyperbilirubinemia and augmented LDH. HbH was positively identified by hemoglobin electrophoresis and hemoglobin cellulose acetate membrance electrophoresis; the other patient had no such abnormalities. Genotypes of 3 patients were of (-a3.7/--SEA)、(aaQs-SEA) and (-SEA), respectively. The activity of P5’N (but not for PK and G-6-PD) in red cell reduced.Conclusions Our study first documented a-thalassaemia with P5’N deficiency. Genetic detection might be essential for the diagnosis of a-thalassaemia.