Heterogeneity in junctional regions of immunoglobulin kappa deleting element rearrangements in B cell leukemias: a new molecular target for detection of minimal residual disease (original) (raw)

Biotechnical Methods Section (BTS): Technical Report

Leukemia volume 11, pages 2200–2207 (1997)Cite this article

Abstract

Virtually all immunoglobulin kappa (IGK) gene deletions are mediated via rearrangements of the so-called kappa deleting element (Kde). Kde rearrangements occur either to V_κ_ gene segments (V_κ_–Kde rearrangements) or to the heptamer recombination signal sequence in the J_κ_–C_κ_ intron. Kde rearrangements were analyzed by the polymerase chain reaction (PCR) and heteroduplex analysis in 130 B-lineage leukemias: 63 precursor-B-acute lymphoblastic leukemias (ALL) and 67 chronic B cell leukemias. To obtain detailed information about Kde rearrangements, we sequenced 109 of the 189 detected junctional regions. V_κ_ gene family usage in the V_κ_–Kde rearrangements in our series of B-lineage leukemias was comparable to V_κ_ gene family usage in functional V_κ_–J_κ_ rearrangements in normal and malignant mature B cells, except for a higher frequency of V_κ_ II family usage in precursor-B-ALL. Junctional region sequencing of the Kde rearrangements in precursor-B-ALL revealed a mean insertion of 4.7 nucleotides and a mean deletion of 9.5 nucleotides, resulting in an extensive junctional diversity, whereas in chronic B cell leukemias the insertion (1.9) and deletion (6.0) were significantly lower. The relatively extensive junctional diversity of the Kde rearrangements in precursor-B-ALL allowed us to design leukemia/patient-specific oligonucleotide probes, which were proven to be useful for detection of minimal residual disease (MRD) with sensitivities of 10−4 to 10−5. Kde rearrangements occur in approximately 50% of precursor-B-ALL cases and are likely to remain stable during the disease course, because Kde rearrangements are assumed to be ‘end-stage’ rearrangements, which cannot easily be replaced by continuing rearrangement processes. These findings indicate that junctional regions of Kde rearrangements in precursor-B-ALL represent new valuable patient-specific PCR targets for detection of MRD.

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Authors and Affiliations

  1. Department of Immunology, University Hospital Rotterdam/Erasmus University Rotterdam, Rotterdam, The Netherlands
    A Beishuizen, MAC de Bruijn, MJ Pongers-Willemse, M-A J Verhoeven, TM Breit, S de Bruin-Versteeg, H Hooijkaas & JJM van Dongen
  2. Dutch Childhood Leukemia Study Group, The Hague, The Netherlands
    ER van Wering & K Hählen
  3. Department of Pediatrics, Subdivision Hematology-Oncology, Sophia Children’s Hospital/Erasmus University Rotterdam, Rotterdam, The Netherlands
    K Hählen

Authors

  1. A Beishuizen
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  2. MAC de Bruijn
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  3. MJ Pongers-Willemse
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  4. M-A J Verhoeven
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  5. ER van Wering
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  6. K Hählen
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  7. TM Breit
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  8. S de Bruin-Versteeg
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  9. H Hooijkaas
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  10. JJM van Dongen
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Beishuizen, A., de Bruijn, M., Pongers-Willemse, M. et al. Heterogeneity in junctional regions of immunoglobulin kappa deleting element rearrangements in B cell leukemias: a new molecular target for detection of minimal residual disease.Leukemia 11, 2200–2207 (1997). https://doi.org/10.1038/sj.leu.2400904

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