Molecular diagnosis using FISH or a PCR-based assay detecting the NUP214-ABL1 fusion can be used to predict the success of the tyrosine kinase inhibitor pathway
Summary of the Invention
T-cell acute lymphoblastic leukemia (T-ALL) accounts for ~15% of newly diagnosed cases of childhood acute lymphoblastic leukemia. Children with T-ALL generally have a poorer prognosis than those with B-ALL. In T-ALL, transcription factors are known to deregulated by chromosomal rearrangements, but mutations in tyrosine kinases have only rarely identified.
VIB researchers have identified extrachromosomal or episomal amplification of ABL1 in T-ALL, which is not normally detectable using conventional cytogenetics. This episomal amplification results of a fusion between NUP214 and ABL1. NUP214-ABL1 results in the expression of a constitutively phosphorylated tyrosine kinase, which is sensitive to the tyrosine kinase inhibitor imatinib.
Therefore, NUP214-ABL1 expression defines a new subgroup that can benefit from imatinib treatment.
Application
Molecular diagnosis of the NUP214-ABL1 expression can be used for patient stratification for therapeutic purposes or selection of clinical trial subjects