AHI1 gene expression levels and BCR-ABL1T315I mutations in chronic myeloid leukemia patients

Abstract

With the availability of molecular monitoring of BCR-ABL1 and the use oftyrosine kinase inhibitors, treatment in chronic myeloid leukemia (CML)is now molecularly focused. Eighty-three samples taken at different time pointsfrom 38 CML patients; were subjected to T315I mutation analysis and gene expressionanalysis of AHI1; a novel gene that is thought to have arole in both BCR-ABL1 mediated leukemic transformation and response to tyrosinekinase inhibitors. Only one patient (2·63%) harbouredthe T315I mutation. While no significant difference in AHI1expression was observed between newly diagnosed CML samples and non-CML controls;CML samples under imatinib therapy had levels significantly higher than bothnewly diagnosed samples and controls. In the first 6 months of imatinib therapy, AHI1expression was found to increase and then gradually decrease. There was nosignificant difference between imatinib responders and non-responders, whiledasatinib caused significantly lower AHI1 levels. It is proposedthat the change in AHI1 expression during CML therapy mightbe under the control of mechanisms independent from BCR-ABL1. AHI1mediated signalling could be better understood by analyzing AHI1gene expression levels in a greater number of patients and concurrently investigatingJAK/STAT and Src family kinases pathways.