Declined presentation Vβ17 T cell clones may respond to ABL-T315I mutation protein in chronic myeloid leukemia in blastic crisis

The clonally expanded T cells identified in cancer patients that specific respond to tumor-associated antigen (TAA) have definite. We previously identified a high frequency of oligoclonal expansion of the Vβ21 T cell subfamily in the peripheral blood (PB) from BCR-ABL positive chronic myeloid leukemia (CML) and B cell acute lymphocytic leukemia (B-ALL) patients, and the TCR Vα13/Vβ21 gene modified T cell maintained anti-CML cytotoxicity. However, little is known whether there are any TCR Vβ specific for the mutant BCR-ABL protein. In this study, we analyzed the TCR β repertoire in PB from two cases with CML in blastic crisis (CML-BC) with ABL gene mutation, case 1 with B-cell resembling lymphoid blast crisis (LBC) contained single kinase domain mutation (T315I), and case 2 with AML resembling myeloid blast crisis (MBC) contained compound-mutant BCR-ABL1 (L387M and T315I). Using RT-PCR and genescan analysis, clonally expanded Vβ17 was identified in samples from both cases. The size of clonal peak in PCR products which indicate the Vβ17 CDR3 length, was all in 181 bp, this indicated that both samples contained Vβ17 clones with similar CDR3 rearrangement. Interesting, the same size clonally expanded Vβ17 T cells was also identified in case 2 at 51 days after HLA-matched sibling hematopoietic stem cell transplantation (HSCT), which is thought from donor origin rather than recipient origin. This result indicated the possibility that the expanded Vβ17 clones may respond to CML associated antigen, particularly for mutant T315I-ABL. Moreover, clonally expanded Vβ18 T cells was identified in case 1, while clonally expanded Vβ15 T cells was found in case 2, this is thought to be individual response to CML associated antigen. In conclusion, our findings showed a identical clonal TCR Vβ17 expansion in CML-BC cases with T315I-ABL mutation. Further investigation will be performed to characterize the function of Vβ17+T cell clone in T315I-ABL mutant CML-BC patients.This study was supported by grants from the NSFC (81270604 and 81400109) The clonally expanded T cells identified in cancer patients that specific respond to tumor-associated antigen (TAA) have definite. We previously identified a high frequency of oligoclonal expansion of the Vβ21 T cell subfamily in the peripheral blood (PB) from BCR-ABL positive chronic myeloid leukemia (CML) and B cell acute lymphocytic leukemia (B-ALL) patients, and the TCR Vα13/Vβ21 gene modified T cell maintained anti-CML cytotoxicity. However, little is known whether there are any TCR Vβ specific for the mutant BCR-ABL protein. In this study, we analyzed the TCR β repertoire in PB from two cases with CML in blastic crisis (CML-BC) with ABL gene mutation, case 1 with B-cell resembling lymphoid blast crisis (LBC) contained single kinase domain mutation (T315I), and case 2 with AML resembling myeloid blast crisis (MBC) contained compound-mutant BCR-ABL1 (L387M and T315I). Using RT-PCR and genescan analysis, clonally expanded Vβ17 was identified in samples from both cases. The size of clonal peak in PCR products which indicate the Vβ17 CDR3 length, was all in 181 bp, this indicated that both samples contained Vβ17 clones with similar CDR3 rearrangement. Interesting, the same size clonally expanded Vβ17 T cells was also identified in case 2 at 51 days after HLA-matched sibling hematopoietic stem cell transplantation (HSCT), which is thought from donor origin rather than recipient origin. This result indicated the possibility that the expanded Vβ17 clones may respond to CML associated antigen, particularly for mutant T315I-ABL. Moreover, clonally expanded Vβ18 T cells was identified in case 1, while clonally expanded Vβ15 T cells was found in case 2, this is thought to be individual response to CML associated antigen. In conclusion, our findings showed a identical clonal TCR Vβ17 expansion in CML-BC cases with T315I-ABL mutation. Further investigation will be performed to characterize the function of Vβ17+T cell clone in T315I-ABL mutant CML-BC patients. This study was supported by grants from the NSFC (81270604 and 81400109)