RUNX1-PDCD6 fusion resulting from a novel t(5;21)(p15;q22) chromosome translocation in myelodysplastic syndrome secondary to chronic lymphocytic leukemia

PLoS One. 2018 Apr 19;13(4):e0196181. doi: 10.1371/journal.pone.0196181. eCollection 2018.

Abstract

Leukemic cells often carry chromosome aberrations which generate chimeric genes of pathogenetic, diagnostic, and prognostic importance. New rearrangements giving rise to novel fusion genes define hitherto unrecognized genetic leukemia subgroups. G-banding, fluorescence in situ hybridization (FISH), and molecular genetic analyses were done on bone marrow cells from a patient with chronic lymphocytic leukemia (CLL) and secondary myelodysplasia. The G-banding analysis revealed the karyotype 46,XX,del(21)(q22)[9]/46,XX[2]. FISH on metaphase spreads with a RUNX1 break apart probe demonstrated that part of RUNX1 (from 21q22) had moved to chromosome band 5p15. RNA sequencing showed in-frame fusion of RUNX1 with PDCD6 (from 5p15), something that was verified by RT-PCR together with Sanger sequencing. Further FISH analyses with PDCD6 and RUNX1 home-made break apart/double fusion probes showed a red signal (PDCD6) on chromosome 5, a green signal on chromosome 21 (RUNX1), and two yellow fusion signals, one on der(5) and the other on der(21). Reassessment of the G-banding preparations in light of the FISH and RNA-sequencing data thus yielded the karyotype 46,XX,t(5;21)(p15;q22)[9]/46,XX[2]. The t(5;21)(p15;q22)/RUNX1-PDCD6 was detected only by performing molecular studies of the leukemic cells, but should be sought after also in other leukemic/myelodysplastic cases with del(21q).

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins / genetics*
  • Calcium-Binding Proteins / genetics*
  • Chromosome Banding
  • Chromosomes, Human, Pair 21
  • Chromosomes, Human, Pair 5
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Middle Aged
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / etiology*
  • Oncogene Proteins, Fusion / genetics*
  • Sequence Analysis, DNA
  • Translocation, Genetic*

Substances

  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • PDCD6 protein, human
  • RUNX1 protein, human

Grants and funding

This work was supported by grants from the Norwegian Radium Hospital Foundation. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.