ABSTRACT
PURPOSE: To analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value. METHOD: A total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers. RESULTS: In total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age <1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P<0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD < 0.1%, and D33 MRD < 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P<0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age <1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P<0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children. CONCLUSIONS: ETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.
ABSTRACT
The patients receiving methotrexate (MTX) treatment are inclined to suffer from cognition impairment, since MTX can induce apoptosis of neurons, while the underlying molecular mechanisms remain unknown. Thus we hypothesized that MTX-induced apoptosis of hippocampal neurons via activating endoplasmic reticulum stress (ERS) pathway, which leads to cognitive impairment in adult rats. In order to confirm our hypothesis, twenty male Sprague-Dawley rats weighting 180-220 g were divided into two groups: the control group (physiological saline) and the MTX60 group (MTX 60 mg/kg). Spatial memory was assayed by the Morris water maze test (MWM). In the mean time, another twenty-four rats were divided into four groups: the control group (physiological saline), MTX60 (MTX, 60 mg/kg), MTX100 (MTX, 100 mg/kg) and MTX250 (MTX, 250 mg/kg). Then, we observed the pathological changes of the hippocampus by hematoxylin-eosin stained. The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were determined by Western blot and immunofluorescence. The apoptosis of neurons were assessed by TUNEL assay. The Morris water maze test showed that MTX induced spatial memory impairment in adult rats (P<0.05). The degenerated or apoptotic neurons were condensed and the number of neurons with nuclear pyknosis increased significantly in hippocampus CA1 area of rats in MTX groups. Additionally, both protein expressions of CHOP and caspase-12 and number of TUNEL positive cells were significantly increased in these MTX groups (P<0.05). The present results suggested that ERS mediated by apoptosis of hippocampal neurons might play an important role in the mechanism of MTX-induced cognitive impairment in adult rats.