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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]