Research Progress on the Role of Tumor-Associated Macrophages in Multiple Myeloma --Review / 中国实验血液学杂志

Bone marrow microenvironment is a highly complex environment surrounding tumor, which plays an important role in the survival, proliferation, drug resistance and migration of multiple myeloma (MM) cells. As an important cellular component in tumor microenvironment, tumor-associated macrophages(TAM) has attracted attention due to its key role in tumor progression and drug resistance. Targeting TAM has shown potential therapeutic value in cancer treatment. In order to clarify the role of macrophages in MM progression, it is necessary to understand the differentiation of TAM and its characteristics of promoting MM. This paper reviews the research progress on how TAM is programmed in MM and the mechanism of TAM promoting tumor development and drug resistance.

NRAS Gene Expression and Its Clinical Significance in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the mutation rate and distribution of Homo sapiens neuroblastoma RAS viral oncogene homolog (NRAS) gene in the patients with acute myeloid leukemia.@*METHODS@#The genomic DNA of bone marrow was screened by polymerase chain reaction (PCR) and sequencing for NRAS mutations. At the same time, the mutations of ASXL1, DNMT3A, TET2, CEBPA, FLT3, IDH2, NPM1 and c-KIT genes were also detected to analyze the relation with NRAS mutations.@*RESULTS@#A total of 11 NRAS mutations were found in 108 patients with initial acute myeloid leukemia and the mutation rate was 10.2%, including 6 cases of G12D, 3 cases of G13D, and 2 cases of G61K. In the mutation group, the peripheral blood leukocyte count was higher (P＜0.05), more likely to occur in the M subtype, and the M subtype was mutually exclusive (P＜0.05). Moreover, the mutant group was more likely to express CD13 than the non-mutation group (P＜0.05), while no statistic difference was found in age, gender, hemoglobin level, platelet count, lactate dehydrogenase level, bone marrow blast, cytogenetics, complete remission rate and overall survival (P＞0.05).@*CONCLUSIONS@#The mutation of NRAS gene has no effect on the prognosis of AML patients.

LY294002 Enhaces Chemosensitivity of K562 Cells to Daunorubicin / 中国实验血液学杂志

OBJECTIVE@#To investigate the proliferation inhibition and pro-apoptosis effect of LY294002 (PI3K/AKT inhibtor) combined with daunorubicin (DNR) on the chronic myeloid leurenia cell line K562 and its possible mechanisms.@*METHODS@#The effect of LY294002 and DNR on the proliferation of K562 cells in different treating time and concentration were measured by MTT assay. The cell cycle was determined by flow cytometry, the mRNA and protein expression of SKP2 , P27, BCL-2 and BAX were determined by RT-PCR and Western blot.@*RESULTS@#LY294002 and DNR were able to inhibit the growth of K562 cells and promote apoptosis in time- and concentration-dependent manner (P＜0.05), both the cell proliferation-inhibiting rate and apoptosis rate in combination therapy group were higher than that in DNR-monotherapy group (P＜0.05). After K562 cells treated by LY294002 combined DNR for 36 h, the cells were statistically significantly reduced in G/M phase (P＜0.05), as compared with control group and DNR group. Compared with DNR group, the cell level of G/G phase rased (P＜0.05) and cell level of S phase decreased (P＞0.05). Compared with DNR group, the expresson of SKP2 and BCL-2 mRNA decreased, and the expression of P27 mRNA increased in the combination therapy group (P＜0.05). The expression of BAX mRNA was not significantly different between different groups. The same result was found in the protein expression.@*CONCLUSION@#LY294002 has the sensibilizative effect on DNR chemotherapy, which may be relative with blocking the cell cycle and inducing cell apoptosis.

Methylation Status and mRNA Expression of DKK-3 and WIF-1 in Acute Myeloid Leukemia Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the promoter methylation status, mRNA expression and clinical significance of DKK-3 and WIF-1 genes in patients with acute myeloid leukemia(AML).</p><p><b>METHODS</b>Methylation specific polymerase chain reaction (MS-PCR) mothod was carried out to detect DKK-3 and WIF-1 gene promoter methylation status in bone marrow specimen from 56 patients with AML and 20 patients with iron deficiency anaemia(IDA) as control; then the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNA expression of DKK-3, WIF-1 gene and β -catenin in the above-mentioned specinens, and their relationship with the clinical features and survival time was analyzed.</p><p><b>RESULTS</b>The promoter methylation rate of DKK-3 and WIF-1 gene in AML patients were significantly higher than that in control group(χ=15.330,P<0.001; χ=17.371,P<0.001). There was no relationship between DKK-3 and WIF-1 gene promoter methylation rate and AML patient's sex, age, clinical typing. The relative expression of DKK-3 and WIF-1 gene mRNA in AML group were 0.840±0.320 and 0.792±0.313, which were lower than those in control group (1.134±0.392 and 1.047±0.334) respectively, the difference was statistically significant (t=3.415,P=0.000; t=3.070, P=0.003). The relative expression of β-catenin mRNA in AML bone marrow specimens in AML group was 0.756±0.304, which was higher than that in control group(0.342±0.105), the difference was statistically significant (t=5.943, P=0.001). The expression of DKK-3 and WIF-1 gene mRNA negatively correlated with β-catenin mRNA(r=-0.543; r=-0.562). Kaplan Meier survival curve analysis showed that overall survival time in AML patients with DKK-3 gene methylation was shorter than that in the AML patients with DKK-3 gene unmethylation(χ=3.957, P=0.042). Futhermore, the orerall survival time in AML patients with WIF-1 gene methylation was also shorter than that in AML patients with WIF-1 gene unmethylation (χ=4.520, P=0.029).</p><p><b>CONCLUSION</b>Wnt/β-catenin signaling pathway is abnormally activated in AML patients, the DKK-3 and WIF-1 gene promoter methylation may be involved in Wnt pathways activation and the pathogenesis of AML.</p>