CD19-Synthetic T Cell Antigen Receptor(STAR)-T in B-cell Malignancies Patients

Biochemical and genetic evidence has implicated two families of protein tyrosine kinases (PTKs), the Src- and Syk-PTKs, in T- and B-cell antigen receptor signaling. ZAP-70 is a member of the Syk-PTKs that associates with the T-cell antigen receptor and undergoes tyrosine phosphorylation following receptor activation. Three tyrosine residues, Tyr-292, -492, and -493, have been identified as sites of phosphorylation following T-cell antigen receptor engagement. Utilizing ZAP-70- and Syk-deficient lymphocytes (Syk-DT40 cells), we provide biochemical and functional evidence that heterologous trans-phosphorylation of Tyr-493 by a Src-PTK is required for antigen receptor-mediated activation of both the calcium and ras pathways. In contrast, cells expressing mutations at Tyr-292 or -492 demonstrate hyperactive T- and B-cell antigen receptor phenotypes. Thus, phosphorylation of ZAP-70 mediates both activation and inactivation of antigen receptor signaling.

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Rearrangements of T-cell antigen receptor delta chain gene in hematologic neoplasms

Blood ◽

10.1182/blood.v74.8.2707.2707 ◽

1989 ◽

Vol 74 (8) ◽

pp. 2707-2712 ◽

Cited By ~ 21

Author(s):

N Asou ◽

T Hattori ◽

M Matsuoka ◽

F Kawano ◽

K Takatsuki

Keyword(s):

T Cell ◽

B Cell ◽

Gene Rearrangement ◽

Antigen Receptor ◽

Chain Gene ◽

Gene Rearrangements ◽

T Cell Antigen Receptor ◽

Cell Antigen Receptor ◽

Cell Antigen ◽

Delta Gene

Abstract Rearrangements of the T-cell antigen receptor (TCR) delta chain gene were studied in primary neoplastic cells from 137 patients with leukemia or lymphoma. TCR delta gene rearrangements or deletions were observed in all 50 T-cell neoplasms: 5 of 8 CD3- T-cell neoplasms showed rearrangements, whereas biallelic deletion of TCR delta gene was the most common pattern in CD3+ T-cell neoplasm (39 of 42 patients). Rearrangements of TCR delta gene were also detected in 23 of 40 immature B-cell leukemias, including 22 of 25 patients with rearrangements of TCR gamma gene, 2 of 17 mature B-cell neoplasms, and 3 of 30 myeloid leukemias. Thus, TCR delta gene rearrangement or deletion is always found in T-cell neoplasms and is frequently found in immature B-cell leukemias associated with TCR gamma gene rearrangement. Furthermore, TCR delta gene rearrangements associated with the germline configuration of the TCR beta, gamma, and immunoglobulin heavy chain genes were observed in two immature T-cell leukemias, suggesting that TCR delta gene rearrangements precede TCR gamma and beta gene rearrangements. These results indicate that an analysis of TCR delta gene rearrangement provides potential tools to establish the clonality of immature T-cell neoplasms and to identify the normal stages of lymphocyte differentiation.

Download Full-text

Rearrangements of T-cell antigen receptor delta chain gene in hematologic neoplasms

Blood ◽

10.1182/blood.v74.8.2707.bloodjournal7482707 ◽

1989 ◽

Vol 74 (8) ◽

pp. 2707-2712

Author(s):

N Asou ◽

T Hattori ◽

M Matsuoka ◽

F Kawano ◽

K Takatsuki

Keyword(s):

T Cell ◽

B Cell ◽

Gene Rearrangement ◽

Antigen Receptor ◽

Chain Gene ◽

Gene Rearrangements ◽

T Cell Antigen Receptor ◽

Cell Antigen Receptor ◽

Cell Antigen ◽

Delta Gene

Rearrangements of the T-cell antigen receptor (TCR) delta chain gene were studied in primary neoplastic cells from 137 patients with leukemia or lymphoma. TCR delta gene rearrangements or deletions were observed in all 50 T-cell neoplasms: 5 of 8 CD3- T-cell neoplasms showed rearrangements, whereas biallelic deletion of TCR delta gene was the most common pattern in CD3+ T-cell neoplasm (39 of 42 patients). Rearrangements of TCR delta gene were also detected in 23 of 40 immature B-cell leukemias, including 22 of 25 patients with rearrangements of TCR gamma gene, 2 of 17 mature B-cell neoplasms, and 3 of 30 myeloid leukemias. Thus, TCR delta gene rearrangement or deletion is always found in T-cell neoplasms and is frequently found in immature B-cell leukemias associated with TCR gamma gene rearrangement. Furthermore, TCR delta gene rearrangements associated with the germline configuration of the TCR beta, gamma, and immunoglobulin heavy chain genes were observed in two immature T-cell leukemias, suggesting that TCR delta gene rearrangements precede TCR gamma and beta gene rearrangements. These results indicate that an analysis of TCR delta gene rearrangement provides potential tools to establish the clonality of immature T-cell neoplasms and to identify the normal stages of lymphocyte differentiation.

Download Full-text