Clinical Characteristics and Prognosis of 27 Patients with Childhood Acute Megakaryoblastic Leukemia.

BACKGROUND The aim of this study was to investigate the clinical features and prognostic factors of childhood acute megakaryoblastic leukemia (AMKL). MATERIAL AND METHODS The data of 27 cases of childhood AMKL admitted from November 2009 to July 2018 were retrospectively analyzed. The survival analysis and prognostic factors were analyzed by Kaplan-Meier method. RESULTS The median follow-up time was 26.4 months in 27 cases, and the complete response rate was 92.31% after 2 chemotherapy courses. Eight patients underwent bone marrow transplantation after 3-6 courses. Five patients died after transplantation, 4 of whom died due to recurrence after transplantation. Of the 27 patients, 10 developed recurrence (37.04%), and 8/10 had recurrence within 1 year. The 3-year overall survival rate and disease-free survival rates were (47±12)% and (36±14)%, respectively. Of the 27 AMKL cases, the 3 with Down syndrome (DS-AMKL) all survived after treatment, and the 3-year overall survival rate was 100%. However, of the other 24 AMKL patients without Down syndrome (non-DS-AMKL), 6 died and 6 abandoned treatment, and the 3-year overall survival rate was only 50%. Univariate analysis showed that 3-year overall survival rate was not correlated to gender, age, number of newly diagnosed white blood cells, karyotype, remission after 2 courses of treatment, and transplant after 3 courses of treatment of childhood AMKL cases. Nevertheless, recurrence and remission after 2 courses of treatment were significantly correlated with 3-year overall survival rate. CONCLUSIONS Children with non-DS-AMKL have a high degree of malignancy and are prone to early recurrence with a poor prognosis, whereas the prognosis of DS-AMKL is relatively good. Recurrence after treatment and remission after 2 courses of treatment are important factors influencing the prognosis of childhood AMKL. Recurrence after transplantation is the leading cause of death in transplantation patients.

[Expression of CCR7 and Tim-3 in Childhood Patients with Acute Lymphoblastic Leukemia and Their Predictive Value for Prognosis].

OBJECTIVE: To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis. METHODS: Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed. RESULTS: The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05). The critical value of CCR7 for diagnosis of recurrence was 45.97%, the sensitivity was 66.7%, the specificity was the 84.5% and the area under ROC curve (AUC) was 0.798 (95CI 0.777-0.939). The critical value of Tim-3 for diagnosis of recurrence was 53.54%, the sensitivity was 73.3%, the specificity was the 80.3% and the AUC was 0.806 (95CI 0.792-0.947). The AUC of the combined detection of CCR7 and Tim-3 was 0.895 (95CI 0.914-0.996), sensitivity 86.6%, specificity 78.9% (P<0.05); There was no significant correlation between CCR7, Tim-3 expression and age, sex, hemoglobin concentration, number of white blood cells, bone marrow blasts, platelets, central nervous system invasion, fusion gene (P>0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05). CONCLUSION: The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

LncRNA SOX2 overlapping transcript acts as a miRNA sponge to promote the proliferation and invasion of Ewing's sarcoma.

Long non-coding RNAs (lncRNAs) function as critical regulator in human cancers. However, the biological regulatory mechanisms of lncRNAs in Ewing's sarcoma are still elusive. This study tries to investigate the clinical significance and pathological role of lncRNA SOX2 overlapping transcript (SOX2OT) in Ewing's sarcoma progression. SOX2OT was identified to be up-regulated in Ewing's sarcoma tissue and cells. In vitro, SOX2OT knockdown suppressed Ewing's sarcoma cells proliferation and invasion, and triggered apoptosis. In vivo xenograft assays, SOX2OT knockdown significantly inhibited Ewing's sarcoma growth. With the help of bioinformatics analysis and luciferase assay, SOX2OT was validated to harbor miR-363, acting as miRNA sponge or competing endogenous RNA (ceRNA). Furthermore, FOXP4 was validated to be the target protein of miR-363. Western blot and RT-PCR confirmed that SOX2OT was positively correlated with FOXP4 protein via sponging miR-363, forming a negative cascade regulation. In conclusion, our study realizes that SOX2OT acted as oncogene in the tumorigenesis of Ewing's sarcoma, suggesting the SOX2OT/miR-363/FOXP4 pathway in Ewing's sarcoma.

Retracted: Long Noncoding RNA SOX2OT Accelerates the Carcinogenesis of Wilms' Tumor Through ceRNA Through miR-363/FOXP4 Axis.

REFERENCES: ATCC. www.lgcstandards-atcc.org/Products/All/CRL-1441.aspx?geo_country=it Memorial Sloan Kettering Cancer Cancer. https://www.mskcc.org/research-advantage/support/technology/tangiblematerial/sk-nep-1-human-ewing-sarcoma-cell-line.

Effects of CDC42 on the proliferation and invasion of gastric cancer cells.

Cell division cycle 42 (CDC42), which is a member of the Rho GTPase family, has been reported to regulate the metastasis of various human cancer cells; however, the role of CDC42 in gastric cancer (GC) remains unclear. The present study aimed to investigate the effects of CDC42 on the proliferation, migration and invasion of GC. Furthermore, the molecular mechanisms underlying the effects of CDC42 on GC were explored. The expression levels of CDC42 in the AGS and SGC7901 human GC cell lines were reduced by RNA interference. Knockdown of CDC42 significantly inhibited the proliferation of AGS and SGC7901 cells, and it was suggested that this inhibitory process may be due to cell cycle arrest at G1/S phase and downregulation of cyclin A, cyclin D1, cyclin E and proliferating cell nuclear antigen. Furthermore, knockdown of CDC42 markedly inhibited the migration and invasion of GC cells, and suppressed the expression of matrix metalloproteinase 9. These results indicated that CDC42 is a key regulator involved in regulating the proliferation, migration and invasion of GC, and it may be considered a potential therapeutic target in GC.

Prognostic value of miR-29a expression in pediatric acute myeloid leukemia.

OBJECTIVES: As a member of miR-29 family, miR-29a can act as either oncogene or tumor suppressor. However, its expression patterns in acute myeloid leukemia (AML) are controversial according to previous studies. Thus, the aim of this study was to determine the expression and clinical significance of miR-29a in pediatric AML. METHODS: Expression levels of miR-29a in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. The prognostic values of miR-29a in pediatric AML were also analyzed. RESULTS: Compared with normal controls, we demonstrated a significantly decreased expression of miR-29a in the bone marrow of pediatric AML patients (P<0.001). The expression levels of miR-29a were significantly lower in French-American-British classification subtype M7 than in other subtypes (P<0.001) and differed significantly across cytogenetic risk groups (P=0.002) with high miR-29a expression among those with favorable karyotypes. Moreover, low miR-29a expression was significantly associated with shorter relapse-free (P<0.001) and overall (P=0.008) survival in pediatric AML patients. Cox proportional hazards multivariate analysis of the univariate predictors identified cytogenetic risk and miR-29a expression as independent prognostic factors for relapse-free survival and overall survival. More interestingly, the prognostic value of miR-29a expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. CONCLUSION: Our data indicate for the first time that the down-regulation of miR-29a was associated with advanced clinical features and poor prognosis of pediatric AML patients, suggesting that miR-29a down-regulation may be used as an unfavorable prognostic marker in pediatric AML.

Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia.

OBJECTIVE: MicroRNA-100 (miR-100), a small noncoding RNA molecule, acts as a tumor suppressor or an oncogene in different cancers. The aberrant expression of this microRNA has been demonstrated as a frequent event in adult patients with acute myeloid leukemia (AML), but little is known for pediatric AML. The aim of this study was to investigate the expression and clinical significance of miR-100 in pediatric AML. METHODS: The expression levels of miR-100 in bone marrow mononuclear cells were detected by real-time quantitative polymerase chain reaction in a cohort of 106 patients with de novo pediatric AML. The prognostic values of miR-100 in pediatric AML were also analyzed. RESULTS: Compared with normal controls, upregulation of miR-100 in the bone marrow of pediatric AML patients with statistically significant differences (P < 0.001) was found. The expression levels of miR-100 were found to be significantly higher in pediatric AML patients with extramedullary disease, with the French-American-British classification subtype M7, and with unfavorable day 7 response to induction chemotherapy (P = 0.008, 0.001 and 0.01, respectively). Moreover, both univariate and multivariate analyses revealed that miR-100 upregulation was associated with poorer relapse-free and overall survival in pediatric AML patients. CONCLUSION: This is the first report demonstrating the upregulation of miR-100 in pediatric AML, and its association with poor relapse-free and overall survival. These results suggest that miR-100 upregulation may be used as an unfavorable prognostic marker in pediatric AML.

Interleukin-8 associates with adhesion, migration, invasion and chemosensitivity of human gastric cancer cells.

AIM: To investigate the relationship between Interleukin-8 (IL-8) and proliferation, adhesion, migration, invasion and chemosensitivity of gastric cancer (GC) cells. METHODS: The IL-8 cDNA was stably transfected into human GC cell line MKN-45 and selected IL-8-secreting transfectants. The expression of IL-8 in human GC cell line KATO-III was inhibited by RNA interference. The expressions of mRNA and protein of IL-8 in GC cells were detected by real-time reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay (ELISA). RESULTS: The overexpression of IL-8 resulted in an increased cell adhesion, migration and invasion, and a significant resistance to oxaliplatin in MKN-45 cells. Inhibition of IL-8 expression with small interfering RNA decreased the adhesion, migration and invasion functions and oxaliplatin resistance in KATO-III cells. IL-8 increased NF-κB and Akt activities and adhesion molecules ICAM-1, VCAM-1, and CD44 expression in GC cells. CONCLUSION: Overexpression of IL-8 promotes the adhesion, migration, invasion, and chemoresistance of GC cells, indicating that IL-8 is an important therapeutic target in GC.