Identification of Heme Oxygenase-1 as a Novel Predictor of Hematopoietic Stem Cell Transplantation Outcomes in Acute Leukemia

Cell Physiol Biochem. 2016;39(4):1495-502. doi: 10.1159/000447852. Epub 2016 Sep 9.

Abstract

Objective: The main aim of this study was to determine the correlation between clinical outcome and heme oxygenase-1 (HO-1) expression before and after hematopoietic stem cell transplantation (HSCT) in acute leukemia.

Methods: HO-1 mRNA levels in 83 patients were measured using qRT-PCR. In a comparative analysis of HO-1 levels in relation to different post-transplant outcomes, the HO-1 threshold, determined via the receiver operating characteristic (ROC) curve, was effectively used to predict clinical relapse and acute graft-versus-host disease (aGVHD). The correlations among clinical relapse, aGVHD and HO-1 expression were analyzed based on this threshold.

Results: Leukemia risk stratification and relative expression of HO-1 before pretreatment had significant effects on clinical relapse. Leukemia risk stratification, relative expression of HO-1 after HSCT and the interval from diagnosis to transplantation had a significant influence on aGVHD. Both relapse and aGVHD appeared to be associated with relative HO-1 expression. The relative expression rate of HO-1 was 1.131-1.186 before pretreatment, and strongly associated with post-transplantation relapse. The relative expression rate of HO-1 was 1.102-1.144 after transplantation, and closely related to aGVHD. ROC curve analysis revealed high specificity and sensitivity of HO-1 expression in predicting relapse and aGVHD after allo-HSCT.

Conclusions: HO-1 expression can be effectively used as a predictor of relapse as well as a diagnostic factor of aGVHD after transplantation for allo-HSCT patients with acute leukemia.

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Bone Marrow / enzymology
  • Bone Marrow / pathology
  • Child
  • Female
  • Gene Expression
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / metabolism
  • Graft vs Host Disease / pathology
  • Hematopoietic Stem Cell Transplantation*
  • Heme Oxygenase-1 / genetics*
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • ROC Curve
  • Recurrence
  • Siblings
  • Time-to-Treatment
  • Transplantation, Homologous
  • Unrelated Donors

Substances

  • Biomarkers
  • RNA, Messenger
  • HMOX1 protein, human
  • Heme Oxygenase-1