Lymphocytic progenitor cell origin and clonal evolution of human B- lineage acute lymphoblastic leukemia

Frederic Davi, Christopher Gocke, Stephen Smith, Jeffrey Sklar

Research output: Contribution to journalArticle

Abstract

At presentation, bone marrow specimens from over 25% of B-lineage acute lymphoblastic leukemias (ALL) display more than two clonal rearrangements of immunoglobulin heavy chain (IgH) genes in Southern blot analyses. Nucleotide sequence analysis has shown predominantly different V(H)DJ(H) junctions among these genes, leading to the frequent description of such cases as oligoclonal leukemias. In the present study, we have analyzed the IgH genes from four patients whose leukemic cells contained different patterns of IgH gene rearrangements between presentation and relapse. Nucleotide sequence analysis of the IgH genes showed that three mechanisms could account for these differences: de novo V(H)DJ(H) rearrangement, V(H) to DJ(H) recombination, and V(H) replacement. In all cases, more than two totally different V(H)DJ(H) rearrangements appeared during evolution of the disease, formally consistent with the conclusion that these tumors were composed of apparently unrelated clones. However, the retention of some of the antigen receptor gene rearrangements, as well as the persistence of a chromosomal marker in two cases, indicated that these leukemias had a monoclonal origin. These findings support the hypothesis that some ALLs arise from a lymphoid progenitor cell at a stage of lymphocyte development before the onset of IgH gene rearrangement. These leukemic lymphocyte progenitors generate malignant daughter cells capable of an in vivo maturation that involves the completion of multiple different IgH rearrangements as well as the modification of preexisting rearrangements by V(H) to DJ(H) recombination or by a V(H) replacement.

Original languageEnglish (US)
Pages (from-to)609-621
Number of pages13
JournalBlood
Volume88
Issue number2
StatePublished - Jul 15 1996
Externally publishedYes

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Clonal Evolution
Immunoglobulin Heavy Chain Genes
Immunoglobulin Heavy Chains
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Stem Cells
Genes
Gene Rearrangement
Genetic Recombination
Sequence Analysis
Lymphocytes
Leukemia
Lymphoid Progenitor Cells
Antigen Receptors
Nucleotides
Southern Blotting
Clone Cells
Bone Marrow
Recurrence
Tumors
Bone

ASJC Scopus subject areas

  • Hematology

Cite this

Lymphocytic progenitor cell origin and clonal evolution of human B- lineage acute lymphoblastic leukemia. / Davi, Frederic; Gocke, Christopher; Smith, Stephen; Sklar, Jeffrey.

In: Blood, Vol. 88, No. 2, 15.07.1996, p. 609-621.

Research output: Contribution to journalArticle

Davi, Frederic ; Gocke, Christopher ; Smith, Stephen ; Sklar, Jeffrey. / Lymphocytic progenitor cell origin and clonal evolution of human B- lineage acute lymphoblastic leukemia. In: Blood. 1996 ; Vol. 88, No. 2. pp. 609-621.
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