Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia

Int J Hematol. 2015 Nov;102(5):579-86. doi: 10.1007/s12185-015-1865-2. Epub 2015 Sep 10.

Abstract

Myeloid-derived suppressor cells (MDSCs) are thought to help provide a cellular microenvironments in many solid tumors, in which transformed cells proliferate, acquire new mutations, and evade host immunosurveillance. In the present study, we found that MDSCs (CD33 + CD11b + HLA-DR(low/neg)) in bone marrow were significantly increased in adult acute myeloid leukemia (AML) patients. MDSCs levels in newly diagnosed AML patients correlated well with extramedullary infiltration and plasma D-dimer levels. Remission rates in the MDSCs > 1500 group and MDSCs < 1500 group were 72.73 and 81.25 %, respectively. No significant differences were found between the two groups. MDSC levels in the complete remission group were significantly decreased after chemotherapy, while in the partial remission and non-remission groups, there were no significant differences. The level of MDSCs in the high minimal residual disease (MRD) group was significantly higher than that in the middle and low MRD groups. High levels of Wilms' Tumor-1 (WT-1) protein were strongly correlated with higher bone marrow MDSC levels. In conclusion, we report here a population of immunosuppressive monocytes in the bone marrow of patients with AML characterized by the CD33(high)CD11b + HLA-DR(low/neg) phenotype. These cells appear to impact the clinical course and prognosis of AML. This data may provide potentially important targets for novel therapies.

Keywords: Adult acute myeloid leukemia (AML); Immune suppression; Minimal residual disease (MRD); Myeloid derived suppressor cells (MDSCs).

MeSH terms

  • Adult
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Female
  • Fibrin Fibrinogen Degradation Products / immunology
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / pathology
  • Neoplasm, Residual
  • Prognosis
  • Tumor Escape*
  • WT1 Proteins / blood
  • WT1 Proteins / immunology

Substances

  • Fibrin Fibrinogen Degradation Products
  • WT1 Proteins
  • WT1 protein, human
  • fibrin fragment D