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

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), diversi...

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Bibliographic Details
Published in:Blood 1993-02, Vol.81 (3), p.775-782
Main Author: KITCHINGMAN, G. R
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Bone Marrow - immunology
Bone Marrow - pathology
Cloning, Molecular - methods
Gene Rearrangement
Genes, Immunoglobulin
Genetic Variation
Hematologic and hematopoietic diseases
Humans
Immunoglobulin Heavy Chains - genetics
Immunoglobulin Joining Region - genetics
Immunoglobulin Variable Region - genetics
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Molecular Sequence Data
Oligodeoxyribonucleotides
Polymerase Chain Reaction - methods
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V81.3.775.775