Immunohistochemical evaluation and prognostic value of monocarboxylate transporter 1 (MCT1) and 4 (MCT4) in T-cell non-Hodgkin lymphoma.

Tumor cells often exhibit the Warburg effect, wherein, they preferentially undergo glycolysis over oxidative phosphorylation for energy production. Monocarboxylate transporter 1 (MCT1) and 4 (MCT4) are critical symporters mediating lactate efflux and preventing intracellular acidification during tumor growth. Numerous studies have focused on inhibiting MCT1 or MCT4 in various cancers. However, its role in T-cell lymphoma (TCL) is not yet investigated owing to the low incidence of TCL. This study was designed to investigate the expression of MCT1/MCT4 in patients with TCL and determine their prognostic value in this cancer. We performed immunohistochemistry to evaluate the expression level of MCT1/MCT4 in 38 TCL tissue samples and then compared their expression among different TCL subgroups, which were formed based on different clinical characteristics. Survival analysis was performed to evaluate the relationship between MCT1/MCT4 expression and both overall survival (OS) and progression-free survival (PFS). Our results revealed that MCT1 and MCT4 expression was significantly increased in TCL tissues compared to the control group. In addition, increased MCT1 expression associated with the female sex, advanced disease stage, increased serum LDH, Ki-67 at ≥ 50%, and intermediate or high-risk groups as categorized by the International Prognostic Index (IPI) score. We also found that increased MCT1 expression may be associated with reduced OS and PFS. In conclusion, MCT1 and MCT4 are overexpressed in patients with TCL and may predict poor prognosis. MCT1 inhibition might be a novel treatment strategy for TCL, and further preclinical trials are required.

[Effect of Decitabine on Megakaryocyte Culture of Steroid-resistant ITP Patients].

OBJECTIVE: To investigate the effect of decitabine and plasma of ITP patients on in vitro cultrue of megakaryocytes in bone marrow of steroid-resistant ITP patients. METHODS: Bone marrow mononuclear cells were isolated from 20 steroid-resistant ITP patients, both methyl cellulose semisolid culture system (to observe and count the number of megakaryocytes colony-forming unit) and liquid culture system (to analysis the expression rate of CD41a(+) cells) were used for megakaryocyte cultrue. The experiments were divided into 4 groups according to the different components of the culture system, group A was control, group B was added with decitabine, group C with ITP plasma, group D with both decitabine and ITP plasma, and the rest of the culture components were the same in the 4 groups except the above-mentioned materials. Morphology of megakaryocytes was observed by inverted and light microscopy. The expression rate of CD41a⁺ cells in culture was analysed by flow cytometric. RESULTS: Different concentration of decitabine showed different effect on megakaryocyte growth of steroid-resistant ITP patients and the optimal concentration to differentiate into megakaryocyte for bone marrow mononuclear cells is 3.0 µmol/L. Compared with group A, both megakaryocyte colony forming units (CFU) and expression rate of CD41a⁺ cells in group B were statistically significantly higher (P < 0.05). As compared with group A, the megakaryocyte colony-forming units in group C decreased with statistically significant difference, while compared with group C, the megakaryocyte colony-forming units in group D obviously increased with statistically significant difference. CONCLUSIONS: Decitabine is able to induce bone marrow mononuclear cells of steroid-resistant ITP patients to differentiate into megakaryocyte and the optimal concentration is 3.0 µmol/L; ITP plasma is able to inhibit the megakaryocyte growth of steroid-resistant ITP patients.