Discovery and Validation of Cell-Surface Protein Mesothelin (msln) As A Novel Therapeutic Target in Aml: Results from the Cog/Nci Target Aml Initiative

In efforts to discover genes uniquely expressed in childhood AML, we performed transcriptomesequencing (RNA-Seq) in pediatric AML and contrasted the expression signature to that in normal marrow hematopoiesis. This effort led to the discovery of over 200 genes that lack expression in normal hematopoietic cells, but are variably expressed in pediatric AML cells. Mesothelin(MSLN) was discovered to be one of the most highly expressed genes in a subset of childhood AML cases (p<10-15).Mesothelin is a cell-surface protein that is expressed onmesothelial cells ofserosal lining. MSLN is over-expressed on a variety of solid tumors, including lung, pancreatic, and ovarian cancers, and is associated with increased malignant transformation, cellular proliferation, and tumor aggressiveness. Given its cell surface expression, MSLN has emerged as an attractive target for immunotherapeutic interventions in solid tumors in adults.