title: AHI1 gene expression levels and BCR-ABL1 T315I mutations in chronic myeloid leukemia patients.
abstract: With the availability of molecular monitoring of BCR-ABL1 and the use of tyrosine kinase inhibitors, treatment in chronic myeloid leukemia (CML) is now molecularly focused. Eighty-three samples taken at different time points from 38 CML patients; were subjected to T315I mutation analysis and gene expression analysis of AHI1; a novel gene that is thought to have a role in both BCR-ABL1 mediated leukemic transformation and response to tyrosine kinase inhibitors. Only one patient (2.63%) harboured the T315I mutation. While no significant difference in AHI1 expression was observed between newly diagnosed CML samples and non-CML controls; CML samples under imatinib therapy had levels significantly higher than both newly diagnosed samples and controls. In the first 6 months of imatinib therapy, AHI1 expression was found to increase and then gradually decrease. There was no significant difference between imatinib responders and non-responders, while dasatinib caused significantly lower AHI1 levels. It is proposed that the change in AHI1 expression during CML therapy might be under the control of mechanisms independent from BCR-ABL1. AHI1 mediated signalling could be better understood by analyzing AHI1 gene expression levels in a greater number of patients and concurrently investigating JAK/STAT and Src family kinases pathways.
authors.affiliation: Department of Medical Genetics, Baskent University, Ankara, Turkey.
authors.forename: Tugce Bulakbasi
authors.initials: TB
authors.lastname: Balci
authors.forename: Feride Iffet
authors.initials: FI
authors.lastname: Sahin
authors.forename: Sema
authors.initials: S
authors.lastname: Karakus
authors.forename: Hakan
authors.initials: H
authors.lastname: Ozdogu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D033942:Adaptor Proteins, Vesicular Transport; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D000069439:Dasatinib; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: C487178:AHI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib