6545

SLC7A4

CAT-4|CAT4|HCAT3|VH;solute carrier family 7 (orphan transporter), member 4;SLC7A4;solute carrier family 7 (orphan transporter), member 4

Ig heavy chain variable region|VH 3 family|cationic amino acid transporter 4|solute carrier family 7 (cationic amino acid transporter, y+ system), member 4|solute carrier family 7 member 4

22q11.21

protein-coding

Somatic mutation (SM) analysis provides a useful tool for understanding the stages at which neoplastic differentiate from normal B-cells. B-cell precursor neoplasms are considered to be somatically premutational. However, the variable frequency of SM of the variable region (VH) genes has been described in cases ofprecursor B-cell acute lymphoblastic leukemia (PB-ALL). To better characterize PB-ALL based on the differentiation stage, we investigated the SM of the VH genes expressed by tumor cells of the surface immunoglobulin (sIg)(-) HBL-3 cell line derived from childhood PB-ALL. In the HBL-3 cell line, the rearranged Ig heavy chain VH gene sequence showed no SM in the complementarity-determining regions of 1, 2, and 3, or in the framework regions of 1, 2, and 3 relative to the putativegermline VH gene sequences. In addition, the VH segment of HBL-3 cells showed nointraclonal sequence heterogeneity, indicating ongoing SM. Our data demonstratedthat HBL-3 cells express unmutated and developmentally regulated rearrangement of VH genes at the stage of B-cell precursor cells. HBL-3 cells, which are derived only from the sIg(-) PB-ALL, showed that SM cannot be recognized in VH genes of tumor cells before the expression of sIg.