We have established a mouse CD4+CD8+ double positive T-cell line (named MOHITO, for MOuse Hematopoietic Interleukin-dependent cell line of T-cell Origin) that has many features of human T-cell acute lymphoblastic leukemia (Notch1 and Jak1 mutation, TCR rearrangement) and is dependent on interleukin-7.
Our results reveal that some JAK1 mutation-positive T-ALLs harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway.
Overall, these results indicate that, in T-cell acute lymphoblastic leukemia, PHF6 mutations are a recurrent genetic abnormality associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214.