We performed a molecular characterization of HS and the corresponding leukemia by methylation arrays and whole-exome sequencing and found a variety of aberrations in both entities with deletions of CDKN2A/B as a recurrent finding.
Since CDKN2A deletion predisposes to development of HS in experimental models, the cytogenetic features of the patient's pre-B ALL may have predisposed to this change in lineage.
These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS.