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

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. Beaver, Brandi R. Walker, Jadwiga M. Labanowska, Nyla A. Heerema, Krzysztof Mrózek, Jennifer A. Woyach, Amy S. Ruppert, Amy Lehman, Hatice Gulcin Ozer, Vincenzo Coppola, Pearlly Yan, John C. Byrd, James S. Blachly and Rosa Lapalombella ()
Additional contact information
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
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
Pearlly Yan: The Ohio State University
John C. Byrd: The Ohio State University
James S. Blachly: The Ohio State University
Rosa Lapalombella: The Ohio State University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26400-x

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