Overexpression of dominant-negative Ikaros 6 isoform is associated with resistance to TKIs in patients with Philadelphia chromosome positive acute lymphoblastic leukemia
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- Published online on: August 16, 2017 https://doi.org/10.3892/etm.2017.4941
- Pages: 3874-3879
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Abstract
The clinical significance of the dominant-negative Ikaros 6 (DN‑IK6) in the treatment of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+‑ALL) with tyrosine kinase inhibitors (TKIs) remains elusive. In the present study, it was demonstrated that DN‑IK6 was overexpressed in B‑cell (B)‑ALL cases compared with T cell‑ALL cases at the mRNA and protein levels. Furthermore, nucleotide sequencing revealed that DN‑IK6 was due to the deletion of IKAROS family zinc finger 1 exons 4‑7. The outcome of patients with Ph+‑B‑ALL with DN‑IK6, and treated with TKIs and hyper-cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen were restrospectively evaluated in a 2 year follow‑up. The results demonstrated that those with the DN isoform exhibited significantly lower incidences of remission, shorter median cumulative incidence of relapse times (P<0.05) and shorter median overall survival times (P<0.05) compared with those without the DN isoform. In conclusion, the results of the present study demonstrated that DN‑IK6 is overexpressed in the majority of patients with Ph+‑ALL, and is significantly associated with resistance to TKI therapy.
