scholarly journals T-Cell Receptor Gamma Chain Alternative Reading Frame Protein Isoform 1

2020 ◽  
Author(s):  
Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5390
Author(s):  
Dyantha I. van der Lee ◽  
Georgia Koutsoumpli ◽  
Rogier M. Reijmers ◽  
Willy Honders ◽  
Rob C. M. de Jong ◽  
...  

Acute myeloid leukemia (AML) is a hematological malignancy caused by clonal expansion of myeloid progenitor cells. Most patients with AML respond to chemotherapy, but relapses often occur and infer a very poor prognosis. Thirty to thirty-five percent of AMLs carry a four base pair insertion in the nucleophosmin 1 gene (NPM1) with a C-terminal alternative reading frame of 11 amino acids. We previously identified various neopeptides from the alternative reading frame of mutant NPM1 (dNPM1) on primary AML and isolated an HLA-A*02:01-restricted T-cell receptor (TCR) that enables human T-cells to kill AML cells upon retroviral gene transfer. Here, we isolated T-cells recognizing the dNPM1 peptide AVEEVSLRK presented in HLA-A*11:01. The TCR cloned from a T-cell clone recognizing HLA-A*11:01+ primary AML cells conferred in vitro recognition and lysis of AML upon transfer to CD8 cells, but failed to induce an anti-tumor effect in immunodeficient NSG mice engrafted with dNPM1 OCI-AML3 cells. In conclusion, our data show that AVEEVSLRK is a dNPM1 neoantigen on HLA-A*11:01+ primary AMLs. CD8 cells transduced with an HLA-A*11:01-restricted TCR for dNPM1 were reactive against AML in vitro. The absence of reactivity in a preclinical mouse model requires further preclinical testing to predict the potential efficacy of this TCR in clinical development.


1986 ◽  
Vol 24 (5) ◽  
pp. 304-308 ◽  
Author(s):  
Konrad Huppi ◽  
Lawrence D'Hoostelaere ◽  
Michael Kiefer ◽  
Michael Steinmetz ◽  
Evelyne Jouvin-Marche

1995 ◽  
Vol 41 (5) ◽  
Author(s):  
Takahiro Isono ◽  
CholJang Kim ◽  
Akira Seto

2020 ◽  
Vol 92 (12) ◽  
pp. 2930-2937
Author(s):  
Mahdi Mohamadi ◽  
Kimia Azarbayjani ◽  
Sayed‐Hamidreza Mozhgani ◽  
Taravat Bamdad ◽  
Ashkan Alamdary ◽  
...  

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1933-1939
Author(s):  
A Tawa ◽  
SH Benedict ◽  
J Hara ◽  
N Hozumi ◽  
EW Gelfand

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.


Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 356-360
Author(s):  
JM Greenberg ◽  
JH Kersey

The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is thought to contribute to the diversity of certain immunoglobulin and T cell receptor gene rearrangements through the addition of random nucleotides at their variable (V)-joining (J) region junctions. An acute lymphoblastic leukemia (ALL) with an immature T cell phenotype (CD7+, CD5+, CD1+/-, CD2+/-, CD3-, CD4-, CD8-) was found to be TdT+ with germline immunoglobulin heavy chain, T cell receptor beta chain, and T cell gamma chain genes. The data indicate that TdT expression can precede T gamma and T beta rearrangement during T lymphoid ontogeny consistent with its proposed association with the T cell receptor rearrangement process. Southern analysis of certain cases of T-ALL may not result in the detection of a monoclonal population of cells.


Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1989-1995 ◽  
Author(s):  
JJ Taylor ◽  
D Rowe ◽  
IK Williamson ◽  
SE Christmas ◽  
SJ Proctor ◽  
...  

Abstract This report describes the development and characterization of a method for the amplification of rearranged V-J segments of the human T-cell receptor gamma chain (TCRG) locus using an adaptation of the polymerase chain reaction (PCR) technique. The technique uses a single pair of ‘consensus’ primers to amplify rearrangements involving the V gamma I subgroup genes, which are common in malignant cells from acute lymphoblastic leukemia (ALL) patients. Using this method we were able to detect rearrangements in the TCRG locus in disease cells from patients with T-cell ALL (12 of 12), common ALL (10 of 14), and Null cell ALL (2 of 2) at presentation. Monoallelic and biallelic rearrangements involving V gamma I subgroup genes were identified by restriction analysis of PCR products from DNA samples from a T-cell leukemic cell line, T-cell clones, and disease cells from patients with ALL of T-and B-cell lineage at presentation. These results confirmed the presence of cell clones within the presentation samples and, in one case, confirmed the persistence of the original malignant cell clone at relapse. This is a rapid and specific method for the detection and characterization of rearrangements of the TCRG locus without recourse to Southern blotting. Therefore, the PCR technique described herein can provide the basis for the study of clonal evolution and minimal residual disease on a high proportion of patients with ALL.


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