scholarly journals Immunoglobulin heavy chain gene VH-D junctional diversity at diagnosis in patients with acute lymphoblastic leukemia

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 775-782 ◽  
Author(s):  
GR Kitchingman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Heavy Chain ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Hematopoietic Progenitor ◽  
Vh Replacement ◽  
Blast Cells ◽  
Ig Heavy Chain

Abstract Acute lymphoblastic leukemia (ALL) represents the clonal outgrowth of transformed hematopoietic progenitor cells. We have found that blast cells in some cases of B-precursor cell ALL contain Ig heavy chain gene rearrangements with considerable diversity at the junctions of the variable (VH), diversity (D), and joining (JH) regions. This diversity consists of heterogeneous nucleotide sequences at the VH-D and, less frequently, the D-JH junctions. In two cases, different VH segments were attached to the same D-JH rearrangement. In all cases studied there was a much higher than expected frequency of nucleotide sequence changes in the VH segment. At least three mechanisms may produce these changes in different cases: (1) continuing rearrangement of the heavy chain gene, in some cases by VH addition to a preexisting D-JH; (2) VH replacement; and (3) an open-and-shut mechanism. These findings suggest that an active VDJ recombinase system is present at the time of transformation in a high percentage of ALLs. An active recombinase in the rapidly growing leukemic cell population could lead to genomic instability.

scholarly journals Immunoglobulin heavy chain gene VH-D junctional diversity at diagnosis in patients with acute lymphoblastic leukemia

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 775-782 ◽  
Author(s):  
GR Kitchingman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Heavy Chain ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Hematopoietic Progenitor ◽  
Vh Replacement ◽  
Blast Cells ◽  
Ig Heavy Chain

Acute lymphoblastic leukemia (ALL) represents the clonal outgrowth of transformed hematopoietic progenitor cells. We have found that blast cells in some cases of B-precursor cell ALL contain Ig heavy chain gene rearrangements with considerable diversity at the junctions of the variable (VH), diversity (D), and joining (JH) regions. This diversity consists of heterogeneous nucleotide sequences at the VH-D and, less frequently, the D-JH junctions. In two cases, different VH segments were attached to the same D-JH rearrangement. In all cases studied there was a much higher than expected frequency of nucleotide sequence changes in the VH segment. At least three mechanisms may produce these changes in different cases: (1) continuing rearrangement of the heavy chain gene, in some cases by VH addition to a preexisting D-JH; (2) VH replacement; and (3) an open-and-shut mechanism. These findings suggest that an active VDJ recombinase system is present at the time of transformation in a high percentage of ALLs. An active recombinase in the rapidly growing leukemic cell population could lead to genomic instability.

scholarly journals Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 536-541 ◽  
Author(s):  
CA Felix ◽  
GH Reaman ◽  
SJ Korsmeyer ◽  
GF Hollis ◽  
PA Dinndorf ◽  
...  
Keyword(s):  
B Cell ◽  
T Cell Receptor ◽  
Heavy Chain ◽  
Light Chain ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Cell Precursor ◽  
Ig Heavy Chain

Abstract We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.

scholarly journals Myeloperoxidase gene expression in blast cells with a lymphoid phenotype in cases of acute lymphoblastic leukemia

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 873-876 ◽  
Author(s):  
S Ferrari ◽  
MT Mariano ◽  
E Tagliafico ◽  
M Sarti ◽  
G Ceccherelli ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Population ◽  
Blot Analysis ◽  
Germ Line ◽  
Lymphoblastic Leukemia ◽  
Cell Populations ◽  
Chain Gene ◽  
Blast Cells ◽  
Chain Gene Rearrangement ◽  
Ig Heavy Chain

By using a cDNA clone of the myeloperoxidase (MPO) gene, we have studied, by Northern blot analysis, the level of MPO mRNA in eight cases of acute lymphoblastic leukemia (ALL). The blast cell populations studied were characterized by morphologic, cytochemical, immunochemical, and molecular criteria. With all the methods used the populations were found to be highly homogeneous and showed a typical lymphoid phenotype. In particular, the Ig heavy-chain gene rearrangement was largely prevalent, and the germ line configuration was almost absent. However, in three of eight cases, high levels of MPO mRNA were detected. The remarkable homogeneity of the cell populations examined suggests that the MPO mRNA observed was present in cellular elements certainly identified as lymphoid. The absence of contamination by myeloid cells was confirmed by the results of Western blot analysis of the proteins of the cell population studied: no MPO protein was detectable. The levels of mRNA observed were high enough to be comparable to those observed in a promyelocytic cell population.

scholarly journals Myeloperoxidase gene expression in blast cells with a lymphoid phenotype in cases of acute lymphoblastic leukemia

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 873-876 ◽  
Author(s):  
S Ferrari ◽  
MT Mariano ◽  
E Tagliafico ◽  
M Sarti ◽  
G Ceccherelli ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Population ◽  
Blot Analysis ◽  
Germ Line ◽  
Lymphoblastic Leukemia ◽  
Cell Populations ◽  
Chain Gene ◽  
Blast Cells ◽  
Chain Gene Rearrangement ◽  
Ig Heavy Chain

Abstract By using a cDNA clone of the myeloperoxidase (MPO) gene, we have studied, by Northern blot analysis, the level of MPO mRNA in eight cases of acute lymphoblastic leukemia (ALL). The blast cell populations studied were characterized by morphologic, cytochemical, immunochemical, and molecular criteria. With all the methods used the populations were found to be highly homogeneous and showed a typical lymphoid phenotype. In particular, the Ig heavy-chain gene rearrangement was largely prevalent, and the germ line configuration was almost absent. However, in three of eight cases, high levels of MPO mRNA were detected. The remarkable homogeneity of the cell populations examined suggests that the MPO mRNA observed was present in cellular elements certainly identified as lymphoid. The absence of contamination by myeloid cells was confirmed by the results of Western blot analysis of the proteins of the cell population studied: no MPO protein was detectable. The levels of mRNA observed were high enough to be comparable to those observed in a promyelocytic cell population.

scholarly journals Rearrangement of immunoglobulin heavy chain genes in T cell acute lymphoblastic leukemia

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 725-729 ◽  
Author(s):  
GR Kitchingman ◽  
U Rovigatti ◽  
AM Mauer ◽  
S Melvin ◽  
SB Murphy ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Heavy Chain ◽  
Germ Line ◽  
Lymphoblastic Leukemia ◽  
Immunoglobulin Heavy Chain ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Immunoglobulin Heavy Chain Genes

Abstract We studied the arrangement of the immunoglobulin heavy chain genes by Southern blot analysis of DNA freshly obtained from marrow blast cells of 14 children with T cell acute lymphoblastic leukemia (T-ALL) using probes to the C mu and JH gene segments: At least one of the C mu-gene alleles was rearranged in three cases. In two of these, one C mu gene had the germ-line configuration and one was rearranged, whereas both alleles were rearranged in the third case. In one case, a rearranged heavy chain gene hybridized to the C mu-region probe, but not to the JH probe, indicating that the entire JH region had been deleted. These results demonstrate that immunoglobulin heavy chain gene rearrangements are not restricted to B lineage lymphoproliferative diseases in humans.

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