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Rare t(X;14)(q28;q32) translocation reveals link between MTCP1 and chronic lymphocytic leukemia

Author

Listed:
  • Janek S. Walker

    (The Ohio State University)

  • Zachary A. Hing

    (The Ohio State University)

  • Steven Sher

    (The Ohio State University)

  • James Cronin

    (The Ohio State University
    The Ohio State University)

  • Katie Williams

    (The Ohio State University)

  • Bonnie Harrington

    (The Ohio State University)

  • Jordan N. Skinner

    (The Ohio State University)

  • Casey B. Cempre

    (The Ohio State University)

  • Charles T. Gregory

    (The Ohio State University)

  • Alexander Pan

    (The Ohio State University)

  • Max Yano

    (The Ohio State University)

  • Larry P. Beaver

    (The Ohio State University)

  • Brandi R. Walker

    (The Ohio State University)

  • Jadwiga M. Labanowska

    (The Ohio State University)

  • Nyla A. Heerema

    (The Ohio State University)

  • Krzysztof Mrózek

    (The Ohio State University)

  • Jennifer A. Woyach

    (The Ohio State University)

  • Amy S. Ruppert

    (The Ohio State University)

  • Amy Lehman

    (The Ohio State University)

  • Hatice Gulcin Ozer

    (The Ohio State University College of Medicine)

  • Vincenzo Coppola

    (The Ohio State University College of Medicine
    The Ohio State University and Arthur G. James Comprehensive Cancer Center)

  • Pearlly Yan

    (The Ohio State University)

  • John C. Byrd

    (The Ohio State University
    The Ohio State University)

  • James S. Blachly

    (The Ohio State University
    The Ohio State University College of Medicine)

  • Rosa Lapalombella

    (The Ohio State University)

Abstract

Rare, recurrent balanced translocations occur in a variety of cancers but are often not functionally interrogated. Balanced translocations with the immunoglobulin heavy chain locus (IGH; 14q32) in chronic lymphocytic leukemia (CLL) are infrequent but have led to the discovery of pathogenic genes including CCND1, BCL2, and BCL3. Following identification of a t(X;14)(q28;q32) translocation that placed the mature T cell proliferation 1 gene (MTCP1) adjacent to the immunoglobulin locus in a CLL patient, we hypothesized that this gene may have previously unrecognized importance. Indeed, here we report overexpression of human MTCP1 restricted to the B cell compartment in mice produces a clonal CD5+/CD19+ leukemia recapitulating the major characteristics of human CLL and demonstrates favorable response to therapeutic intervention with ibrutinib. We reinforce the importance of genetic interrogation of rare, recurrent balanced translocations to identify cancer driving genes via the story of MTCP1 as a contributor to CLL pathogenesis.

Suggested Citation

  • Janek S. Walker & Zachary A. Hing & Steven Sher & James Cronin & Katie Williams & Bonnie Harrington & Jordan N. Skinner & Casey B. Cempre & Charles T. Gregory & Alexander Pan & Max Yano & Larry P. Bea, 2021. "Rare t(X;14)(q28;q32) translocation reveals link between MTCP1 and chronic lymphocytic leukemia," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26400-x
    DOI: 10.1038/s41467-021-26400-x
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    References listed on IDEAS

    as
    1. Dan A. Landau & Eugen Tausch & Amaro N. Taylor-Weiner & Chip Stewart & Johannes G. Reiter & Jasmin Bahlo & Sandra Kluth & Ivana Bozic & Mike Lawrence & Sebastian Böttcher & Scott L. Carter & Kristian , 2015. "Mutations driving CLL and their evolution in progression and relapse," Nature, Nature, vol. 526(7574), pages 525-530, October.
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