Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors / 中华血液学杂志

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Effects of Quercetin on Expression of Akt, p-Akt, Bcl-2 and Bax and Apoptosis of Hippocampal Neurons Cultured in High Glucose / 中国康复理论与实践

@#Objective To explore the possible mechanism of quercetin on apoptosis of hippocampal neurons cultured in high glucose. Methods Hippocampus was obtained from newborn 24 hours Sprague-Dawley rats and then primarily cultured.Then hippocampal neurons were divided into normal control group,high glucose group,quercetin group,quercetin+Akt inhibitor group and Akt agonist group.After each group was cultured in different conditioned medium for 72 hours,they were detected the apoptosis of neurons with flow cytometry,and the expression of Akt,p-Akt,Bcl-2 and Bax with Western blotting.Results Compared with the normal control group,the apoptosis rate of hippocampal neurons increased significantly(P<0.01),and p-Akt/Akt and Bcl-2/Bax decreased significantly(P<0.01)in the high glucose group.Compared with the high glucose group,the apoptosis rates of hippocampal neurons decreased significantly(P<0.01),and p-Akt/Akt and Bcl-2/Bax increased significantly(P<0.01)in the quercetin group and the Akt agonist group.Compared with the quercetin+Akt inhibi-tor group,the apoptosis rate of hippocampal neurons decreased significantly(P<0.01),and p-Akt/Akt and Bcl-2/Bax increased significantly (P<0.01)in the quercetin group.Conclusion Quercetin could reduce the apoptosis of hippocampal neurons cultured in high glucose,which may be achieved by increasing the phosphorylation of Akt protein in Akt signal pathway,and then increasing the expression of Bcl-2 and in-hibiting the expression of Bax.