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Degree of focal immunoglobulin heavy chain locus deletion as a measure of B-cell tumor purity

Leukemia volume 27, pages 2067–2068 (2013)Cite this article

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During normal B-cell development there are sequential rearrangements in the immunoglobulin heavy chain (IgH) locus, each of which results in the joining of two non-contiguous sequences, with deletion of intervening sequences.1 First, in pro-B cells, a diversity region (DH) and a joining region (JH) are rearranged to form a DHJH sequence on both alleles of IgH locus. Subsequently, after both DHJH joining events are completed, a variable region (VH) can be juxtaposed to the DHJH sequence to form a VHDHJH sequence in at least one but sometimes in both IgH loci. As a result of the deletions resulting from these rearrangements, clonal B cells or plasma cells will have unique patterns of deletion in the VH…DH…JH region of the IgH loci. At later stages of B-cell development, IgH switch recombination can reposition the VHDHJH sequence near downstream constant regions (CH). As a result, clonal B cells or plasma cells that have undergone IgH switch recombination also will have clonal patterns of deletion in the CH region of the IgH locus. Often the B-cell specific deletions described above are large enough to be detected as a homozygous copy number loss using comparative genomic hybridization or single-nucleotide polymorphism arrays. Therefore, copy number changes in the IgH locus have the potential to provide a measure of contamination of clonal B or plasma cells with other cells.

Isolation of tumor cells from bone marrow aspirates of patients with MM can achieve a purity of 90–95% by bead selection of cells expressing CD138. However, as the fraction of tumor cells from bone marrow aspirates of patients with MGUS can be 1–2 logs lower than for MM, substantial contamination of purified MGUS tumor cells with non-tumor cells is a significant problem that needs to be rigorously addressed when analyzing purified tumor cells.

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Authors and Affiliations

  1. Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ, USA

    P L Bergsagel

  2. Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    W M Kuehl

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  1. P L Bergsagel
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  2. W M Kuehl
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Correspondence to P L Bergsagel.

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Bergsagel, P., Kuehl, W. Degree of focal immunoglobulin heavy chain locus deletion as a measure of B-cell tumor purity. Leukemia 27, 2067–2068 (2013). https://doi.org/10.1038/leu.2013.139

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