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- Title
Rare t(X;14)(q28;q32) translocation reveals link between MTCP1 and chronic lymphocytic leukemia.
- Authors
Walker, Janek S.; Hing, Zachary A.; Sher, Steven; Cronin, James; Williams, Katie; Harrington, Bonnie; Skinner, Jordan N.; Cempre, Casey B.; Gregory, Charles T.; Pan, Alexander; Yano, Max; Beaver, Larry P.; Walker, Brandi R.; Labanowska, Jadwiga M.; Heerema, Nyla A.; Mrózek, Krzysztof; Woyach, Jennifer A.; Ruppert, Amy S.; Lehman, Amy; Ozer, Hatice Gulcin
- 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. Some genes that are part of balanced translocations are reported as drivers for tumourigenesis. Here, the authors report a translocation involving MTCP1 in chronic lymphocytic leukemia and show that MTCP1 overexpression leads to the disease in a murine model.
- Subjects
CHRONIC lymphocytic leukemia; CHROMOSOMAL translocation; IMMUNOGLOBULIN heavy chains; CANCER genes; B cells; LOCUS (Genetics); T cells; LOCUS (Mathematics)
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-26400-x