Characteristics of the TCR Vβ repertoire in imatinib-resistant chronic myeloid leukemia patients with ABL mutations

Abstract

Diversity in the T cell receptor (TCR) repertoire provides a miniature defense ability for the T cell immune system that may be related to tumor initiation and progression. Understanding the T cell immune status of leukemia patients is critical for establishing specific immunotherapies. Previous studies have reported abnormal TCR repertoires and clonally expanded TCR V T cells in chronic myeloid leukemia in chronic phase (CP-CML). In this study, we investigated the distribution and clonality of the TCR V repertoire in 4 cases with imatinib-resistant CML in blast crisis (BC-CML) with abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase domain mutations (KDMs). Examination of TCR V expression and clonality was performed by reverse transcription-polymerase chain reaction (RT-PCR) and GeneScan analysis. Significantly skewed TCR V repertoires were observed in BC-CML patients with different KDMs, and 4 to 8 oligoclonally expanded TCR V subfamilies could be identified in each sample. Intriguingly, a relatively highly expanded V9 clone with the same length as complementarity-determining region 3 (CDR3) (139 bp) was found in all three CML patients in lymphoid blast crisis (LBC-CML) who had different KDMs, but the clone was not detected in the only CML patient in myeloid blast crisis (MBC-CML). In conclusion, restricted TCR V repertoire expression and decreased clone complexity was a general phenomenon observed in the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency of these patients. In addition, clonally expanded V9 T cell clones may indicate a specific immune response to leukemia-associated antigens in LBC-CML patients.T cell repertoire, chronic myeloid leukemia, blast crisis, imatinib resistance, BCR-ABL mutation Citation:

A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ T cells in patients with acute myeloid leukemia

“…Previous studies have shown different proliferation patterns of TCR subfamily T cells between different subtypes and different disease statuses in leukemia at the molecular level . In this study, we also found a different distribution pattern of TCR Vβ subfamily T cells, particularly PD‐1+ Vβ subfamily T cells, between M5 and the favorable prognosis subtype M3.…”

“…Previous studies have shown different proliferation patterns of TCR subfamily T cells between different subtypes and different disease statuses in leukemia at the molecular level. 40,41 In this study, we also found a different distribution pattern of TCR V subfamily T cells, particularly PD-1+ V subfamily T cells, between M5 and the favorable prognosis subtype M3. However, there are only 3 cases with M5, so it is hard to perform the statistical analysis; we only observed the trends of alteration of PD-1+ V +T cells in both group, providing preliminary data regarding the association of PD-1+V + CD8+ T cells and the prognosis of AML.…”

Persistent donor derived Vδ4 T cell clones may improve survival for recurrent T cell acute lymphoblastic leukemia after HSCT and DLI

“…The labeled runoff PCR products (2 μl) were heat denatured at 94°C for 4 min with 9.5 μl formamide (Hi-Di Formamide, ABI, USA) and 0.5 μl Size Standards (GenenScan-500-LIZ™ PerkinElmer, ABI). The samples were then loaded in a 310 POP-4™ gel (Performance Optimized Polymer-4, ABI, USA) and resolved by electrophoresis with a 310 DNA sequencer (ABI, Perkin Elmer) for size and fluorescence intensity analysis using GeneScan software [39–41]. …”

Generation of V α13/β21+T cell specific target CML cells by TCR gene transfer

“…We previously observed the oligoclonal TCR Vβ21 gene at a high frequency (26.4%) in CML using RT-PCR-Genescan technology, and in vitro oligoclonal Vβ21 T cells from cord blood could be induced by K562 cells, CML cells,as well as a BCR-ABL fusion peptide. Furthermore, the emergence of oligoclonal Vβ21 T cells was investigated in relapse CML patients post allo-HSCT after DLI, and clonality was retained until complete remission [14, 31, 32]. This evidence suggests that clonally expanded Vβ21 T cells may have an anti-CML function.…”