scholarly journals Comparison of T cell receptor alpha, beta, and gamma gene rearrangement and expression in T cell acute lymphoblastic leukemia.

1988 ◽  
Vol 81 (4) ◽  
pp. 989-996 ◽  
Author(s):  
J Hara ◽  
S H Benedict ◽  
E Champagne ◽  
T W Mak ◽  
M Minden ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Receptor Alpha ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Alpha Beta ◽  
Cell Receptor Alpha

Ig Heavy Chain Gene Rearrangements in T-Cell Acute Lymphoblastic Leukemia Exhibit Predominant Dh6-19 and Dh7-27 Gene Usage, Can Result in Complete V-D-J Rearrangements, and Are Rare in T-Cell Receptor β Lineage

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4079-4085 ◽  
Author(s):  
Tomasz Szczepański ◽  
Marja J. Pongers-Willemse ◽  
Anton W. Langerak ◽  
Wietske A. Harts ◽  
Annemarie J.M. Wijkhuijs ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Significant Proportion ◽  
Cell Receptor ◽  
Gene Rearrangements ◽  
Gene Deletions ◽  
Cell Acute Lymphoblastic Leukemia

Rearranged IGH genes were detected by Southern blotting in 22% of 118 cases of T-cell acute lymphoblastic leukemia (ALL) and involved monoallelic and biallelic rearrangements in 69% (18/26) and 31% (8/26) of these cases, respectively. IGH gene rearrangements were found in 19% (13/69) of CD3− T-ALL and in 50% of TCRγδ+ T-ALL (12/24), whereas only a single TCRβ+ T-ALL (1/25) displayed a monoallelicIGH gene rearrangement. The association with the T-cell receptor (TCR) phenotype was further supported by the striking relationship between IGH and TCR delta (TCRD) gene rearrangements, ie, 32% of T-ALL (23/72) with monoallelic or biallelicTCRD gene rearrangements had IGH gene rearrangements, whereas only 1 of 26 T-ALL with biallelic TCRD gene deletions contained a monoallelic IGH gene rearrangement. Heteroduplex polymerase chain reaction (PCR) analysis with Vh and Dh family-specific primers in combination with a Jhconsensus primer showed a total of 39 clonal products, representing 7 (18%) Vh-(Dh-)Jh joinings and 32 (82%) Dh-Jh rearrangements. Whereas the usage of Vh gene segments was seemingly random, preferential usage of Dh6-19 (45%) and Dh7-27 (21%) gene segments was observed. Although the Jh4 and Jh6 gene segments were used most frequently (33% and 21%, respectively), a significant proportion of joinings (28%) used the most upstream Jh1 and Jh2 gene segments, which are rarely used in precursor-B-ALL and normal B cells (1% to 4%). In conclusion, the high frequency of incomplete Dh-Jh rearrangements, the frequent usage of the more downstream Dh6-19 and Dh7-27 gene segments, and the most upstream Jh1 and Jh2 gene segments suggests a predominance of immature IGH rearrangements in immature (non-TCRβ+) T-ALL as a result of continuing V(D)J recombinase activity. More mature β-lineage T-ALL with biallelic TCRD gene deletions apparently have switched off their recombination machinery and are less prone to cross-lineageIGH gene rearrangements. The combined results indicate thatIGH gene rearrangements in T-ALL are postoncogenic processes, which are absent in T-ALL with deleted TCRD genes and completed TCR alpha (TCRA) gene rearrangements.

scholarly journals Temporal and lineage-specific control of T cell receptor alpha/delta gene rearrangement by T cell receptor alpha and delta enhancers.

1994 ◽  
Vol 179 (6) ◽  
pp. 1913-1921 ◽  
Author(s):  
P Lauzurica ◽  
M S Krangel
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Cell Subset ◽  
Cell Receptor ◽  
Receptor Alpha ◽  
Specific Step ◽  
Delta Gene ◽  
Alpha Beta ◽  
Cell Receptor Alpha

To analyze the regulation of gene rearrangement at the T cell receptor (TCR) alpha/delta locus during T cell development, we generated transgenic mice carrying a human TCR delta gene minilocus. We previously showed that the presence of the TCR delta enhancer (E delta) within the J delta 3-C delta intron was required to activate a specific step (V-D to J) of transgene rearrangement, and that rearrangement was activated equivalently in the precursors of alpha beta and gamma delta T cells. To further explore the role of transcriptional enhancers in establishing the developmental pattern of gene rearrangement at the TCR alpha/delta locus, we substituted the TCR alpha enhancer (E alpha) in place of E delta within the transgenic minilocus. We found that V-D-J rearrangement of the E alpha+ minilocus was restricted to the alpha beta T cell subset. Further, we found that although V-D-J rearrangement of the E delta+ minilocus was initiated in the fetal thymus by day 14.5, V-D-J rearrangement of the E alpha+ minilocus did not occur until fetal day 16.5. Finally, whereas V-D-J rearrangement of the E delta+ minilocus is essentially completed within the triple negative population of postnatal thymocytes, V-D-J rearrangement of the E alpha+ minilocus is only initiated late within this population. Since the properties of minilocus rearrangement under the control of E delta and E alpha parallel the properties of V delta-D delta-J delta and V alpha-J alpha rearrangement at the endogenous TCR alpha/delta locus, we conclude that these enhancers play an important role in orchestrating the developmental program of rearrangements at this locus.

Ig Heavy Chain Gene Rearrangements in T-Cell Acute Lymphoblastic Leukemia Exhibit Predominant Dh6-19 and Dh7-27 Gene Usage, Can Result in Complete V-D-J Rearrangements, and Are Rare in T-Cell Receptor β Lineage

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4079-4085 ◽  
Author(s):  
Tomasz Szczepański ◽  
Marja J. Pongers-Willemse ◽  
Anton W. Langerak ◽  
Wietske A. Harts ◽  
Annemarie J.M. Wijkhuijs ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Significant Proportion ◽  
Cell Receptor ◽  
Gene Rearrangements ◽  
Gene Deletions ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Rearranged IGH genes were detected by Southern blotting in 22% of 118 cases of T-cell acute lymphoblastic leukemia (ALL) and involved monoallelic and biallelic rearrangements in 69% (18/26) and 31% (8/26) of these cases, respectively. IGH gene rearrangements were found in 19% (13/69) of CD3− T-ALL and in 50% of TCRγδ+ T-ALL (12/24), whereas only a single TCRβ+ T-ALL (1/25) displayed a monoallelicIGH gene rearrangement. The association with the T-cell receptor (TCR) phenotype was further supported by the striking relationship between IGH and TCR delta (TCRD) gene rearrangements, ie, 32% of T-ALL (23/72) with monoallelic or biallelicTCRD gene rearrangements had IGH gene rearrangements, whereas only 1 of 26 T-ALL with biallelic TCRD gene deletions contained a monoallelic IGH gene rearrangement. Heteroduplex polymerase chain reaction (PCR) analysis with Vh and Dh family-specific primers in combination with a Jhconsensus primer showed a total of 39 clonal products, representing 7 (18%) Vh-(Dh-)Jh joinings and 32 (82%) Dh-Jh rearrangements. Whereas the usage of Vh gene segments was seemingly random, preferential usage of Dh6-19 (45%) and Dh7-27 (21%) gene segments was observed. Although the Jh4 and Jh6 gene segments were used most frequently (33% and 21%, respectively), a significant proportion of joinings (28%) used the most upstream Jh1 and Jh2 gene segments, which are rarely used in precursor-B-ALL and normal B cells (1% to 4%). In conclusion, the high frequency of incomplete Dh-Jh rearrangements, the frequent usage of the more downstream Dh6-19 and Dh7-27 gene segments, and the most upstream Jh1 and Jh2 gene segments suggests a predominance of immature IGH rearrangements in immature (non-TCRβ+) T-ALL as a result of continuing V(D)J recombinase activity. More mature β-lineage T-ALL with biallelic TCRD gene deletions apparently have switched off their recombination machinery and are less prone to cross-lineageIGH gene rearrangements. The combined results indicate thatIGH gene rearrangements in T-ALL are postoncogenic processes, which are absent in T-ALL with deleted TCRD genes and completed TCR alpha (TCRA) gene rearrangements.

Lymphoid development in mice congenitally lacking T cell receptor alpha beta-expressing cells

Science ◽  
1992 ◽  
Vol 256 (5062) ◽  
pp. 1448-1452 ◽  
Author(s):  
K. Philpott ◽  
J. Viney ◽  
G Kay ◽  
S Rastan ◽  
E. Gardiner ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Lymphoid Development ◽  
Receptor Alpha ◽  
Alpha Beta ◽  
Cell Receptor Alpha

scholarly journals Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1933-1939
Author(s):  
A Tawa ◽  
SH Benedict ◽  
J Hara ◽  
N Hozumi ◽  
EW Gelfand
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Cell Receptor ◽  
Gene Rearrangements ◽  
Gamma Chain ◽  
Beta Gene

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.

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