Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia

Genes Chromosomes Cancer. 2017 Nov;56(11):800-809. doi: 10.1002/gcc.22483. Epub 2017 Aug 11.

Abstract

High PRDM16 (also known as MEL1) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1, which is an alternatively spliced transcript of MECOM (also known as EVI1). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression (PRDM16/ABL1 ratio ≥ 0.010). High PRDM16 expression significantly correlated with DNMT3A (43% vs. 15%, P < 0.001) and NPM1 (43% vs. 21%, P = 0.010) mutations and partial tandem duplication of KMT2A (22% vs. 1%, P < 0.001). Remarkably, high-PRDM16-expression patients were frequent in the noncomplete remission group (48% vs. 21%, P = 0.002). Overall survival (OS) was significantly worse in high-PRDM16-expression patients than in low-PRDM16-expression patients (5-year OS, 18% vs. 34%; P = 0.002). This trend was observed more clearly among patients aged <65 years (5-year OS, 21% vs. 50%; P = 0.001), particularly in FLT3-ITD-negative patients in the intermediate cytogenetic risk group (5-year OS, 25% vs. 59%; P = 0.009). These results suggest that high PRDM16 expression is a significant predictive marker for poor prognosis in adult AML patients, similar to pediatric AML patients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mutation
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • DNMT3A protein, human
  • KMT2A protein, human
  • NPM1 protein, human
  • Nuclear Proteins
  • PRDM16 protein, human
  • Transcription Factors
  • Nucleophosmin
  • Myeloid-Lymphoid Leukemia Protein
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Histone-Lysine N-Methyltransferase
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3