Frequent microsatellite instability and BAX mutations in T cell acute lymphoblastic leukemia cell lines.

Allelic status of the BAT26 and BAT25 loci was examined in 117 leukemia/lymphoma cell lines consisting of 44 B-lymphoid lineage cell lines, 30 T-lymphoid cell lines and 43 myeloid cell lines to define the lineage specificity of microsatellite instability (MSI) in hematological malignancies. Seventeen (15%) cell lines were defined as having MSI. The incidence of MSI was significantly (P < 0.01) higher in cell lines of lymphoid lineage (15/74; 20%) than in those of myeloid lineage (2/43; 5%). In the cell lines of lymphoid lineage, the incidence of MSI in T cell acute lymphoblastic leukemia (T-ALL) (11/30; 37%) was significantly (P < 0.01) higher than those in B-lineage malignancies (4/44; 9%). The 17 cell lines with MSI were subjected to the mutation analysis of the coding microsatellites in 13 candidate genes. Frameshift mutations were most frequently detected in the BAX gene (14/17, 82%), while the hMSH3, hMSH6, TGFbetaRII, DRP and IGFIIR genes were less frequently mutated (24-47%). The present result indicates that MSI is involved in the development and/or progression of lymphoid malignancies, especially of T-ALL, through the inactivation of BAX and several other genes.