scholarly journals Rearranged T-cell receptor beta genes represent powerful targets for quantification of minimal residual disease in childhood and adult T-cell acute lymphoblastic leukemia

Leukemia ◽  
2004 ◽  
Vol 18 (4) ◽  
pp. 709-719 ◽  
Author(s):  
M Brüggemann ◽  
V H J van der Velden ◽  
T Raff ◽  
J Droese ◽  
M Ritgen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
T Cell Receptor Beta ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Receptor Beta ◽  
Minimal Residual

scholarly journals Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 356-360
Author(s):  
JM Greenberg ◽  
JH Kersey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Beta Chain ◽  
Gamma Chain ◽  
T Cell Receptor Beta ◽  
Receptor Beta

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.

scholarly journals Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Blood ◽  
1995 ◽  
Vol 86 (2) ◽  
pp. 692-702 ◽  
Author(s):  
EJ Steenbergen ◽  
OJ Verhagen ◽  
EF van Leeuwen ◽  
H van den Berg ◽  
AE von dem Borne ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Southern Blot ◽  
T Cell Receptor ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
First Relapse ◽  
Minimal Residual

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.

scholarly journals Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 356-360 ◽  
Author(s):  
JM Greenberg ◽  
JH Kersey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Beta Chain ◽  
Gamma Chain ◽  
T Cell Receptor Beta ◽  
Receptor Beta

Abstract 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.

Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4520-4526 ◽  
Author(s):  
Aihong Li ◽  
Jianbiao Zhou ◽  
David Zuckerman ◽  
Montse Rue ◽  
Virginia Dalton ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Minimal Residual Disease ◽  
T Cell Receptor ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Gene Rearrangements ◽  
Childhood All ◽  
Minimal Residual

AbstractImmunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements provide clonal markers useful for diagnosis and measurement of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We analyzed the sequences of Ig and TCR gene rearrangements obtained at presentation and relapse in 41 children with ALL to study clonal stability, which has important implications for monitoring MRD, during the course of the disease. In 42%, all original Ig and/or TCR sequences were conserved. In 24%, one original sequence was preserved but the other lost, and in 14% the original sequences were conserved with new sequences identified at relapse. In 20% only new sequences were found at relapse. Using primers designed from the novel relapse sequences, the relapse clone could be identified as subdominant clones in the diagnostic sample in 8 of 14 patients. Alteration of these clonal gene rearrangements is a common feature in childhood ALL. MRD detection should include multiple gene targets to minimize false-negative samples or include also multicolor flow cytometry. In some cases the leukemic progenitor cell might arise earlier in lineage before DHJH recombination but retain the capacity to further differentiate into cells capable of altering the pattern of Ig and/or TCR rearrangements. (Blood. 2003;102:4520-4526)

Sign in / Sign up

Export Citation Format

Share Document