Targeting CD33 for acute myeloid leukemia therapy.

BACKGROUND: The aim of this study was to analyze the level of CD33 expression in patients with newly diagnosed AML and determine its correlation with clinical characteristics. METHODS: Samples were collected for analysis from AML patients at diagnosis. We evaluated the level of CD33 expression by flow cytometry analysis of bone marrow. Chi-square or t- tests were used to assess the association between the high and low CD33 expression groups. Survival curves were generated by the Kaplan-Meier and Cox regression model method. RESULTS: In this study we evaluated the level of CD33 expression in de novo patients diagnosed from November 2013 until January 2019. The mean value of 73.4% was used as the cutoff for the two groups. Statistical analysis revealed that 53 of the 86 (61.2%) AML patients were above the mean. Although there was no statistical significance between CD33 expression level and gene mutation, FLT3 mutation (P = 0.002) and NPM1 mutation (P = 0.001) were more likely to be seen in the high CD33 group. The overall survival (OS) was worse in the high CD33 group (39.0 m vs. 16.7 m, x2 = 13.06, P < 0.001). The Cox survival regression display that the CD33 is independent prognostic marker (HR =0.233,p = 0.008). Univariate analysis showed that the high expression of CD33 was an unfavorable prognostic factor. Of the 86 patients, CD33-high was closely related to the patients with normal karyotype (x2 = 4.891,P = 0.027), high white blood cell count (WBC, t = 2.804, P = 0.007), and a high ratio of primitive cells (t = 2.851, P = 0.005). CONCLUSIONS: These findings provide a strong rationale for targeting CD33 in combination with chemotherapy, which can be considered a promising therapeutic strategy for AML.

[Metformin Induces Apoptosis of Human Multiple Myeloma Cell U266 through the Mitochondrial Apoptotic Pathway].

OBJECTIVE: Metformin (Met) can inhibit the proliferation of tumor cells in vitro, its effects on multiple myeloma and action mechanisms have been not yet understood. The purpose of this study was to investigate the effect and molecular mechanism of metformin on human myeloma cells U266. METHODS: U266 cells were treated with different concentration of Met, the MTT was used to detect cell proliferation, the PI staining was used to detect the cell cycle, and the protein expression of BCL-2 family and the release of cytochrome C were assessed by Western blot. RESULTS: Metformin could inhibit the proliferation of U266 cell in a time- and concentration- dependent manner. The U266 cells were arrested in G1/G0 phase after metformin treatment for 48 h, as compared with non-treated U266 cells. The proteins expression of BCL-2 and BCL-XL was down-regulated and the protein expression of BAX was up-regulated. The released of cytochrome C from mitochondria to cytoplasm was increased, and protein splicing of PARP was also enhanced. CONCLUSION: Metformin can inhibit the cell proliferation and induce U266 cell apoptosis through the mitochondrial apoptotic pathway.