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The t(12;21)(p13;q22) ETV6- RUNX1 gene fusion is one of the most common chromosomal translocation in childhood acute lymphoblastic leukemia ( ALL). It is associated with favorable prognosis. The identification of the genomic sequence of the breakpoint flanking regions of the ETV6- RUNX1 translocation should be the best strategy to monitor minimal residual disease ( MRD) in patients with ETV6- RUNX1-positive ALL. In this study, the ETV6- RUNX1 translocation was sequenced by next-generation sequencing ( NGS) in 26 patients with ETV6- RUNX1-positive ALL and re-sequenced by using the Sanger method. Interestingly, the three-way translocation, including ETV6- RUNX1, was detected in five patients. Four of them relapsed during or after therapy, while 21 patients without the three-way translocation were still in remission ( P < 0.0001). The three-way translocation pattern was identical between the diagnosis and relapse samples in three patients, excluding one patient ( SCMC-001245). The relapse samples retained the translocation of ETV6- RUNX1 relative to the three-way translocation t(8;12;21) at diagnosis, suggesting that the three-way translocation might be an important risk factor for relapse in patients with ETV6- RUNX1-positive ALL and should be further studied. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor--binding protein 7 (IGFBP7) has been identified as a tumor suppressor in solid tumors. In acute leukemia, the role of IGFBP7 is largely unknown. The authors used quantitative reverse transcriptase--polymerase chain reaction (qRT-PCR) to investigate the expression level of IGFBP7 gene in bone marrow (BM) specimen from 66 children with acute myeloid leukemia (AML) at different stages and in 30 nonleukemia patients as control. Furthermore, U937 cells were transfected with siRNA-2 of IGFBP7 (as U937R) for 24 hours. Coculture experiment was performed to explore the impact of IGFBP7 gene in U937 cell adhesion, invasion, and migration in existing ECV304 cells, which mimicked the interaction between AML cells and endothelial cells. IGFBP7 expression at the initial diagnosed stage and relapse of AML was significantly higher than that of control ( P < .001). The viable cell percentage in transfected cell was significantly decreased by 42%% compared with control groups ( P < .01). The percentage for U937R cells adherent to ECV304 cells was significantly lower than the control groups ( P < .01). Matrigel study to quantify the invasive potential showed that U937R migrated to the lower chamber were significantly less than those in the parental control groups ( P < .01). In summary, IGFBP7 aberrantly overexpressed in majority of AML at diagnosis and upon relapsed, but not at remission stage. IGFBP7 plays a positive contributing role in the interaction between leukemia cells and microenvironment, which may promote the leukemic cells'' adhesion, invasion, and migration. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to observe the prognosis of pediatric patients with E2A-PBX1-positive acute lymphoblastic leukemia (ALL) from the treatment with the CCLG-ALL2008 protocol., Design and Methods: Three hundred and forty-nine Chinese pediatric patients with pre-B-cell ALL were enrolled in this study from December 2008 to September 2013. Of these, 20 patients with E2A-PBX1 expression and 223 without the gene expression were stratified into two cohorts. Clinical and biological characteristics and 5-year event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS) were analyzed and compared between these two groups., Results: The E2A-PBX1 fusion transcript was detected in 20 of 349 (5.7%) patients. Compared with the gene-negative subgroup, patients with E2A-PBX1 were younger in age but did not show significant differences in white blood cell (WBC) count or gender distribution at primary diagnosis. Moreover, there were more inferior karyotypes detected in the E2A-PBX1 subgroup ( P =0.035). With the CCLG-ALL2008 treatment protocol, patients with E2A-PBX1 showed a favorable treatment response with lower minimal residual disease (MRD) levels (<10 -4 ) at time point 1 (TP1, P =0.039) but no superior steroid response or histological remission. We also observed a promising survival outcome, with a 5-year EFS reaching 95.0%±4.9% versus 66.3%±3.9% in the gene-negative group ( P =0.039). However, we did not find significant differences in RFS ( P =0.061) and OS ( P =0.113)., Conclusion: Our data provided clinical observation of Chinese pediatric patients. Patients with E2A-PBX1-positive ALL benefited well from the CCLG-ALL2008 protocol, a risk-based intensified treatment trial, with lower levels of MRD and longer RFS duration though they had no favorable characteristics at primary diagnosis., Competing Interests: The authors report no conflicts of interest in this work.

The present study aimed to explore the function of miR‑34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation‑specific PCR were performed to measure the levels of miR‑34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR‑34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR‑34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR‑34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR‑34b levels in prednisone‑sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit‑8 assay showed that transfection of miR‑34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5‑aza‑2‑deoxycytidine significantly enhanced miR‑34b expression levels and decreased the methylation status of its promoter in HL‑60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR‑34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR‑34b on cell proliferation. It was also indicated that the expression of miR‑34b in ALL patients may affect their response to early treatments.

Autoimmune hemolytic anemia (AIHA) is a rare disease in children, and its clinical severity varies. To better understand disease manifestation and treatment outcome, we analyzed 68 children diagnosed as AIHA for clinical characteristics, laboratory findings, and treatment outcomes. Data show that primary AIHA accounted for 39.7% of all patients, whereas secondary AIHA accounted for 60.3%. Among them, Evans syndrome (ES) accounted for 20 cases (29.4%). Average hemoglobin was lower in the 1-year or below age group than in the above 1-year age group, combined-antibody group than single-antibody group, and IgM-contained group than non-IgM-contained group (P<0.05 for all). The duration of therapy in the ES group was longer than that in the AIHA-only group (P<0.05). During the follow-up period, 29 cases (29/45, 64.4%) remained in continuous remission. In total, 35.6% of patients relapsed after first complete remission and 56.3% of them still showed good response to glucocorticoid after relapse. There was no difference in the duration of therapy or relapse rate between the intravenous immunoglobulin (IVIG)-treatment group and the non-IVIG-treatment group. In conclusion, the severity of anemia correlates with age and serologic types of direct antiglobulin test. Glucocorticoid is efficacious for AIHA regardless of whether it is a first attack or relapse in this cohort of young patients. ES needs longer treatment duration. IVIG does not improve the outcome of AIHA.