Label-free quantitative proteomics reveals differentially expressed proteins in high risk childhood acute lymphoblastic leukemia.

ABSTRACT

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. B-ALL is the most common type in pediatric ALL. Risk stratification is critical for setting on chemo-therapeutic regimen that has great impact on the survival rate. But the risk allocation schemas at present were not satisfied. We performed a proteomic study expecting to figure out the critical altered proteins which can indicate the risk rank. We depicted 86 differently expressed proteins in the high-risk childhood B-ALL, and 35 proteins were predicted to have directive interactions. We validated five identified proteins by immunoblot using specimens same as proteomics, and others different from that. We found the differently expressed proteins participated in pre-mRNA spicing, DNA damage response, and stress response which indicated different events happened in the high risk B-ALL. Our result provided new information for children B-ALL. It might aid more accurate risk stratification and might also be valuable to find new therapeutic targets. BIOLOGICAL SIGNIFICANCE: To our knowledge, this is the first proteomic analysis comparing the differentially expressed proteins between high risk and low risk of childhood B-ALL by a label-free quantitative proteomics. We found in high risk B-ALL, the aberrant evens happened in pre-mRNA splicing, DNA damage response, and stress response. This study reveals new insights in the high risk B-ALL, and might also be valuable to identify the high-risk more accurately, as well as to find new therapeutic targets.