Prognostic Significance of Mixed-Lineage Leukemia (MLL) Gene Detected by Real-Time Fluorescence Quantitative PCR Assay in Acute Myeloid Leukemia

Med Sci Monit. 2016 Aug 26:22:3009-17. doi: 10.12659/msm.900429.

Abstract

BACKGROUND The overall prognosis of acute myeloid leukemia (AML) patients with mixed-lineage leukemia (MLL) gene-positivity is unfavorable. In this study, we evaluated the expression levels of the MLL gene in AML patients. MATERIAL AND METHODS We enrolled 68 MLL gene-positive patients out of 433 newly diagnosed AML patients, and 216 bone marrow samples were collected. Real-time fluorescence quantitative PCR (RQ-PCR) was used to precisely detect the expression levels of the MLL gene. RESULTS We divided 41 patients into 2 groups according to the variation of MRD (minimal residual disease) level of the MLL gene. Group 1 (n=22) had a rapid reduction of MRD level to ≤10^-4 in all samples collected in the first 3 chemotherapy cycles, while group 2 (n=19) had MRD levels constantly >10^-4 in all samples collected in the first 3 chemotherapy cycles. Group 1 had a significantly better overall survival (p=0.001) and event-free survival (p=0.001) compared to group 2. Moreover, the patients with >10^-4 MRD level before the start of HSCT (hematopoietic stem cell transplantation) had worse prognosis and higher risk of relapse compared to patients with ≤10^-4 before the start of HSCT. CONCLUSIONS We found that a rapid reduction of MRD level to ≤10^-4 appears to be a prerequisite for better overall survival and event-free survival during the treatment of AML. The MRD levels detected by RQ-PCR were basically in line with the clinical outcome and may be of great importance in guiding early allogeneic HSCT (allo-HSCT) treatment.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Disease-Free Survival
  • Female
  • Fluorescence
  • Hematopoietic Stem Cell Transplantation / methods
  • Histone-Lysine N-Methyltransferase / biosynthesis
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / biosynthesis
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Neoplasm, Residual
  • Prognosis
  • Real-Time Polymerase Chain Reaction / methods
  • Recurrence
  • Transcriptome

Substances

  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase