Abstract
B-cell acute lymphoblastic leukemia is the most common malignant tumor in children. About 10–15% of patients will relapse with a 5-year OS of 57.5% for the past 20 years. As tumor microenvironment plays an important role in the disease process, many types of immunotherapy are approached. New immunotherapies including CAR-T cells have been developed for refractory B-ALL treatment. However, CAR-T treatment faces several problems, including loss of the target antigen and in vivo T-cell persistence. Here, we analyzed the tumor microenvironment of pediatric B-ALL patients in TARGET database. Using Cox analysis and PPI network, we finally sorted out the DAP10 gene. We found that DAP10 was hardly expressed in leukemic B cells. DAP10 was downregulated in B-ALL compared with normal individuals, and low expression level of DAP10 predicted poor survival. Furthermore, we found the tumor microenvironment was different in DAP10 high and low expression children. The CD8+ T cells might be hard to activate and more likely to suffer from exhaustion in DAP10 lowly expressed children. In conclusion, our results showed that DAP10 was a well biomarker to indicate the prognosis and tumor microenvironment in pediatric B-ALL. The treatment strategy of immunotherapy for the leukemic children with DAP10 lowly expressed should be adjusted if needed.
Highlights
Acute lymphoblastic leukemia (ALL) is the most common malignant tumor in children characterized by the proliferation of immature lymphoid cells, and B-cell lineage (BALL) accounts for the majority
We found that DAP10 was downregulated in B-ALL compared with normal individuals, and low expression level of DAP10 predicted poor survival
We removed the cases of T-ALL, mixed-ALL, no survival data, or those above 18 years old according to the clinical data. e cases merely containing transcriptional data of blood sample or relapsed bone marrow sample were not enrolled in the analysis
Summary
Acute lymphoblastic leukemia (ALL) is the most common malignant tumor in children characterized by the proliferation of immature lymphoid cells, and B-cell lineage (BALL) accounts for the majority. Over the past few decades, there have been significant improvements in the survival outcomes of pediatric ALL. Analyses showed the 5-year overall survival (OS) rate for children was from 86% to 90% [1, 2]. Despite these improvements, 10–15% of patients will relapse and approximately 55% of those will relapse again [3, 4]. In contrast to the improvement of survival in newly diagnosed patients, the outcome of relapsed patients remains poor with a 5-year OS of 57.5% and has not changed significantly for the past 20 years [5, 6]. Many studies have demonstrated that patients with high immune infiltration would improve clinical
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