MLL-rearranged acute myeloid leukemia: Influence of the genetic partner in allo-HSCT response and prognostic factor of MLL 3' region mRNA expression

Eur J Haematol. 2018 May;100(5):436-443. doi: 10.1111/ejh.13037. Epub 2018 Mar 1.

Abstract

Objective: MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML).

Methods: Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes. Risk stratification and association of MLL genetic partner and gene expression to overall survival, in the context of received therapy, were performed.

Results: MLLr cohort showed to have an OS more similar to intermediate-risk AML. Type of MLL genetic partner showed to be relevant in allo-HSCT response; having MLLT1 and MLLT3, a better benefit from it. Expression of MLL-3' region, EVI1 and FLT3, showed association with OS in patients undergoing allo-HSCT.

Conclusion: We show that the MLL genetic partner could have implications in allo-HSCT response, and we propose three genes whose expression could be useful for the prognosis of this leukemia in patients undergoing allo-HSCT: 3' region of MLL, EVI1, and FLT3.

Keywords: MLL; AML; EVI1; allo-HSCT.

MeSH terms

  • 3' Untranslated Regions*
  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement*
  • Hematopoietic Stem Cell Transplantation
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Kaplan-Meier Estimate
  • Karyotype
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • MDS1 and EVI1 Complex Locus Protein / genetics
  • Male
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger*
  • Translocation, Genetic
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • KMT2A protein, human
  • MDS1 and EVI1 Complex Locus Protein
  • MECOM protein, human
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3