Therapy-related Myeloid Leukemia With the Translocation t(8;19)(p11;q13) Leading to a KAT6A-LEUTX Fusion Gene

Anticancer Res. 2021 Apr;41(4):1753-1760. doi: 10.21873/anticanres.14940.

Abstract

Background/aim: The chromosome translocation t(8;19)(p11;q13) has been reported in only six acute myeloid leukemia (AML) patients. We here present the genetic and clinical features of the seventh AML case with this aberration.

Materials and methods: Cytogenetic and molecular genetic investigations were performed on leukemic bone marrow cells from a patient with therapy-related AML.

Results: A t(8;19)(p11;q13) was found leading to an in-frame fusion of exon 16 of the lysine acetyltransferase 6A gene (KAT6A) from 8p11 with exon 2 of the leucine twenty homeobox gene (LEUTX) from 19q13 resulting in expression of the otherwise silent LEUTX gene in the leukemic cells. The KAT6A-LEUTX protein is predicted to act as a histone acetyltransferase at its amino-terminal-KAT6A moiety but as a homeobox transcription factor at the LEUTX-carboxyl-terminal moiety.

Conclusion: The present case is the second therapy-related AML, and the third AML overall, in which both a t(8;19)(p11;q13) and its molecular result, a KAT6A-LEUTX fusion gene, are described. The t(8;19)(p11;q13)/KAT6A-LEUTX deregulates transcription and induces leukemogenesis.

Keywords: Acute myeloid leukemia; KAT6A; KAT6A-LEUTX; LEUTX; chromosome translocation; fusion gene; histone acetyltransferase; homeobox gene; t(8;19)(p11;q13).

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Chemoradiotherapy / adverse effects*
  • Chromosomes, Human, Pair 19*
  • Chromosomes, Human, Pair 8*
  • Female
  • Gene Expression Regulation, Leukemic
  • Gene Fusion*
  • Histone Acetyltransferases / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / etiology*
  • Leukemia, Myeloid, Acute / genetics
  • Translocation, Genetic*
  • Treatment Outcome
  • Uterine Cervical Neoplasms / therapy

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • LEUTX protein, human
  • Histone Acetyltransferases
  • KAT6A protein, human