T-cell receptor delta/alpha rearrangements in lymphoid neoplasms

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1073-1083 ◽  
Author(s):  
MJ Dyer
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Cell Precursor ◽  
Lymphoid Neoplasms ◽  
Histiocytic Lymphoma ◽  
T Cell Malignancies

Abstract Rearrangements within the T-cell receptor (TCR)delta/alpha locus were analyzed in a wide variety of lymphoid neoplasms by eight DNA probes specific for TCR J delta, J alpha and C alpha segments. In all 11 T- cell malignancies, rearrangement and/or deletion of TCR delta was detected irrespective of the stage of maturation of the tumor. The organization of TCR delta correlated with the phenotype of the tumor: In “prethymic” T-cell acute lymphocytic leukemia (ALL), TCR delta was the only TCR gene to be rearranged. More mature T cell malignancies expressing CD4 together with CD3 showed deletion of both alleles of TCR delta, suggestive of TCR V alpha-J alpha rearrangement. All 43 B-cell tumors expressing surface immunoglobulin (sIg), including two cases of adult B-cell ALL, had germline configuration of TCR delta/alpha. In contrast, all 17 B-cell precursor ALLs (null, common, and pre-B-cell ALLs) had rearrangement and/or deletion of TCR delta/alpha. A single case of “histiocytic” lymphoma also showed biallelic deletion of TCR delta. Oligoclonal rearrangements of Ig and TCR genes were observed in two cases of B-cell precursor ALL and in one case of T-cell lymphoblastic lymphoma. Patterns of such “aberrant” TCR rearrangement were similar to those observed in T-lineage malignancies. In particular, seven of eight cases of B-cell precursor ALL and the histiocytic lymphoma which demonstrated biallelic TCR delta deletion, (suggestive of a V alpha-J alpha rearrangement) had clonal TCR beta rearrangement. These data support the hypothesis that supposedly aberrant rearrangements of the TCR genes may follow the same developmental controls as found in T-cell differentiation, despite the lack of evidence for further commitment to the T-cell lineage. TCR delta rearrangement is a useful marker of clonality of immature T-cell tumors which may have only this gene rearranged but is not specific to the T-cell lineage.

scholarly journals T-cell receptor delta/alpha rearrangements in lymphoid neoplasms

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1073-1083
Author(s):  
MJ Dyer
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Cell Precursor ◽  
Lymphoid Neoplasms ◽  
Histiocytic Lymphoma ◽  
T Cell Malignancies

Rearrangements within the T-cell receptor (TCR)delta/alpha locus were analyzed in a wide variety of lymphoid neoplasms by eight DNA probes specific for TCR J delta, J alpha and C alpha segments. In all 11 T- cell malignancies, rearrangement and/or deletion of TCR delta was detected irrespective of the stage of maturation of the tumor. The organization of TCR delta correlated with the phenotype of the tumor: In “prethymic” T-cell acute lymphocytic leukemia (ALL), TCR delta was the only TCR gene to be rearranged. More mature T cell malignancies expressing CD4 together with CD3 showed deletion of both alleles of TCR delta, suggestive of TCR V alpha-J alpha rearrangement. All 43 B-cell tumors expressing surface immunoglobulin (sIg), including two cases of adult B-cell ALL, had germline configuration of TCR delta/alpha. In contrast, all 17 B-cell precursor ALLs (null, common, and pre-B-cell ALLs) had rearrangement and/or deletion of TCR delta/alpha. A single case of “histiocytic” lymphoma also showed biallelic deletion of TCR delta. Oligoclonal rearrangements of Ig and TCR genes were observed in two cases of B-cell precursor ALL and in one case of T-cell lymphoblastic lymphoma. Patterns of such “aberrant” TCR rearrangement were similar to those observed in T-lineage malignancies. In particular, seven of eight cases of B-cell precursor ALL and the histiocytic lymphoma which demonstrated biallelic TCR delta deletion, (suggestive of a V alpha-J alpha rearrangement) had clonal TCR beta rearrangement. These data support the hypothesis that supposedly aberrant rearrangements of the TCR genes may follow the same developmental controls as found in T-cell differentiation, despite the lack of evidence for further commitment to the T-cell lineage. TCR delta rearrangement is a useful marker of clonality of immature T-cell tumors which may have only this gene rearranged but is not specific to the T-cell lineage.

scholarly journals High prevalence of T-cell receptor V delta 2-(D)-D delta 3 or D delta 1/2-D delta 3 rearrangements in B-precursor acute lymphoblastic leukemias

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1834-1840 ◽  
Author(s):  
A Biondi ◽  
P Francia di Celle ◽  
V Rossi ◽  
G Casorati ◽  
G Matullo ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Lymphoproliferative Disorders ◽  
Cell Precursor ◽  
Gene Assembly ◽  
Lymphoid Malignancies ◽  
High Prevalence

Abstract Rearrangement of the immunoglobulin (Ig) and T-cell receptor (TcR) genes generally has been considered a useful marker of B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangements of Ig and TcR genes have been commonly reported in the most immature lymphoid malignancies, mainly in B-cell precursor acute lymphoblastic leukemia (ALL). To better characterize the nature of this lineage promiscuity, we have analyzed the configuration of the TcR delta locus in 75 B-precursor ALL. The large majority of cases (87%) displayed a rearrangement or deletion at the delta locus. Among the 57 nondeletional rearrangements, two patterns were predominant and both appeared to derive from partial joining: a V delta-(D)-D delta 3 (32/57) and a D delta 1/2-D delta 3 (11/57) type. A single V delta gene (V delta 2) appeared to be involved in the first type of rearrangement. These findings are at variance with T-ALL, where rearrangements 5′ to V delta 2 are usually found. It remains to be elucidated whether this incomplete attempt of V delta 2 gene assembly is related to the neoplastic event or represents a physiologic predisposition occurring during early stages of the normal lymphocyte differentiation.

The incidence of clonal T-cell receptor rearrangements in B-cell precursor acute lymphoblastic leukemia varies with age and genotype

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2254-2261 ◽  
Author(s):  
Caren Brumpt ◽  
Eric Delabesse ◽  
Kheira Beldjord ◽  
Frederic Davi ◽  
Jean-Michel Cayuela ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Cell Precursor ◽  
Increased Risk ◽  
Ontogenic Development

B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) are increasingly treated on risk-adapted protocols based on presenting clinical and biological features. Residual molecular positivity of clonal immunoglobulin (IG) and T-cell receptor (TCR) rearrangements allows detection of patients at an increased risk of relapse. If these rearrangements are to be used for universal follow-up, it is important to determine the extent to which they are informative in different BCP-ALL subsets. We show thatIGH V-D-J rearrangements occur in 89% of 163 BCP-ALL, with no significant variation according to age or genotype (BCR-ABL, TEL-AML1, MLL-AF4, and E2A-PBX1). In contrast,TCRG rearrangements, which occur in 60% of patients overall, are frequent in BCR-ABL and TEL-AML1, are less so in MLL-AF4, and are virtually absent in infants aged predominantly from 1 to 2 years and in E2A-PBX1 ALLs. Incidence of the predominant TCRD Vδ2-Dδ3 rearrangement decreases with age but is independent of genotype. These differences are not due to differential recombination activating gene activity, nor can they be explained adequately by stage of maturation arrest. Analysis of MLL-AF4 BCP-ALL is in keeping with transformation of a precursor at an early stage of ontogenic development, despite the adult onset of the cases analyzed. We postulate that the complete absence of TCRG rearrangement in E2A-PBX1 cases may result from deregulated E2A function. These data also have practical consequences for the use ofTCR clonality for the molecular follow-up of BCP-ALL.

High prevalence of T-cell receptor V delta 2-(D)-D delta 3 or D delta 1/2-D delta 3 rearrangements in B-precursor acute lymphoblastic leukemias

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1834-1840 ◽  
Author(s):  
A Biondi ◽  
P Francia di Celle ◽  
V Rossi ◽  
G Casorati ◽  
G Matullo ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Lymphoproliferative Disorders ◽  
Cell Precursor ◽  
Gene Assembly ◽  
Lymphoid Malignancies ◽  
High Prevalence

Rearrangement of the immunoglobulin (Ig) and T-cell receptor (TcR) genes generally has been considered a useful marker of B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangements of Ig and TcR genes have been commonly reported in the most immature lymphoid malignancies, mainly in B-cell precursor acute lymphoblastic leukemia (ALL). To better characterize the nature of this lineage promiscuity, we have analyzed the configuration of the TcR delta locus in 75 B-precursor ALL. The large majority of cases (87%) displayed a rearrangement or deletion at the delta locus. Among the 57 nondeletional rearrangements, two patterns were predominant and both appeared to derive from partial joining: a V delta-(D)-D delta 3 (32/57) and a D delta 1/2-D delta 3 (11/57) type. A single V delta gene (V delta 2) appeared to be involved in the first type of rearrangement. These findings are at variance with T-ALL, where rearrangements 5′ to V delta 2 are usually found. It remains to be elucidated whether this incomplete attempt of V delta 2 gene assembly is related to the neoplastic event or represents a physiologic predisposition occurring during early stages of the normal lymphocyte differentiation.

Characterization of immunoglobulin and T-cell receptor gene patterns in B-cell precursor acute lymphoblastic leukemia of childhood.

1990 ◽  
Vol 8 (3) ◽  
pp. 431-442 ◽  
Author(s):  
C A Felix ◽  
D G Poplack ◽  
G H Reaman ◽  
S M Steinberg ◽  
D E Cole ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Leukemic Cells ◽  
Cell Precursor

Immunoglobulin (Ig) and T-cell receptor (TCR) genes were examined in the lymphoblasts of 70 children with immunophenotypically defined B-cell precursor acute lymphoblastic leukemia (ALL). The most frequent genes to rearrange were Ig heavy (H) chain (93%) and TCR delta (79%), followed by TCR gamma (49%), Ig kappa and/or lambda light (L) chain (46%), TCR alpha (46%), and TCR beta (29%). Thus, despite their putative "B-cell precursor" lineage, these leukemias manifest a remarkably high incidence of TCR gene rearrangements. While certain patterns predominate, there is considerable heterogeneity in Ig and TCR genotypes in this disease. No significant associations were found between Ig and TCR genotype and commonly used prognostic factors including age, sex, race, WBC, French-American-British (FAB) subtype, or cytogenetics. However, the lymphoblasts of three of six patients who failed to achieve initial remission had germline patterns of every Ig and TCR gene, a genotype not observed in the leukemic cells from any of the 64 patients who achieved complete remission (p2 = .0007). This study suggests that particular Ig and TCR genotypes may be of clinical relevance in childhood B-cell precursor ALL. The finding of rearranged TCR genes in a large proportion of cases raises fundamental questions about early lineage commitment and lymphocyte differentiation along B-cell and T-cell pathways.

The incidence of clonal T-cell receptor rearrangements in B-cell precursor acute lymphoblastic leukemia varies with age and genotype

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2254-2261 ◽  
Author(s):  
Caren Brumpt ◽  
Eric Delabesse ◽  
Kheira Beldjord ◽  
Frederic Davi ◽  
Jean-Michel Cayuela ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Cell Precursor ◽  
Increased Risk ◽  
Ontogenic Development

Abstract B-cell precursor acute lymphoblastic leukemias (BCP-ALLs) are increasingly treated on risk-adapted protocols based on presenting clinical and biological features. Residual molecular positivity of clonal immunoglobulin (IG) and T-cell receptor (TCR) rearrangements allows detection of patients at an increased risk of relapse. If these rearrangements are to be used for universal follow-up, it is important to determine the extent to which they are informative in different BCP-ALL subsets. We show thatIGH V-D-J rearrangements occur in 89% of 163 BCP-ALL, with no significant variation according to age or genotype (BCR-ABL, TEL-AML1, MLL-AF4, and E2A-PBX1). In contrast,TCRG rearrangements, which occur in 60% of patients overall, are frequent in BCR-ABL and TEL-AML1, are less so in MLL-AF4, and are virtually absent in infants aged predominantly from 1 to 2 years and in E2A-PBX1 ALLs. Incidence of the predominant TCRD Vδ2-Dδ3 rearrangement decreases with age but is independent of genotype. These differences are not due to differential recombination activating gene activity, nor can they be explained adequately by stage of maturation arrest. Analysis of MLL-AF4 BCP-ALL is in keeping with transformation of a precursor at an early stage of ontogenic development, despite the adult onset of the cases analyzed. We postulate that the complete absence of TCRG rearrangement in E2A-PBX1 cases may result from deregulated E2A function. These data also have practical consequences for the use ofTCR clonality for the molecular follow-up of BCP-ALL.

Developmental process of the T-cell receptor α and δ gene assembly in B-cell precursor acute lymphoblastic leukaemia

1991 ◽  
Vol 78 (2) ◽  
pp. 180-186 ◽  
Author(s):  
Junichi Hara ◽  
Keisei Kawa-Ha ◽  
Yoshihiro Takihara ◽  
Keiko Yumura-Yagi ◽  
Shigehiko Ishihara ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Lymphoblastic Leukaemia ◽  
B Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukaemia ◽  
Developmental Process ◽  
Cell Receptor ◽  
Cell Precursor ◽  
Gene Assembly
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