Identification of a t(X;17)(q28;q21) generating a KANSL1-MTCP1 gene fusion leading to dysregulated expression of MTCP1 in acute myeloid leukemia

Genes Chromosomes Cancer. 2020 Jul;59(7):417-421. doi: 10.1002/gcc.22840. Epub 2020 Mar 20.

Abstract

Chromosomal translocations and generating fusion genes are closely associated with disease initiation and progression in acute myeloid leukemia (AML). In this study, we identified a novel t(X;17)(q28;q21) chromosomal rearrangement in a patient with acute monocytic leukemia. Using RNA-sequencing, we identified a KANSL1-MTCP1 and a KANSL1-CMC4 fusion gene. 5'-UTR sequences of the KANSL1 gene were found to become fused upstream of the coding sequence region of the MTCP1 and CMC4 genes, respectively, resulting in an aberrantly high expression of these genes. Functional studies revealed that overexpression of the MTCP1 gene induced an increased cell proliferation and partial blockage of cell differentiation, suggesting that the aberrant expression of MTCP1 is of critical importance in leukemogenesis.

Keywords: KANSL1-MTCP1; acute myeloid leukemia; fusion gene; overexpression; t(X;17)(q28;q21).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Adult
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Nuclear Proteins / genetics*
  • Oncogene Fusion*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Translocation, Genetic*

Substances

  • 5' Untranslated Regions
  • MTCP1 protein, human
  • NSL1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins