BACKGROUND: Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert CD4+CD25− conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters. METHODS: Thirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR. RESULTS: Both IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05). CONCLUSION: Higher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.
Bone Marrow ; Disease Progression ; Hematologic Neoplasms ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase* ; Karyotype* ; Leukemia, Myeloid, Acute* ; Leukocytes ; Phenotype* ; Platelet Count ; Prognosis ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes ; T-Lymphocytes, Regulatory

Background: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched ­CD19+IgD−CD27+ on-class-switched ­CD19+IgD+CD27+ memory B cell subsets and ­CD19 + CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. Methods: This cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. Results: The frequency of ­­CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both ­CD19+IgD−CD27+ class-switched and ­­CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of ­CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. Conclusion This study is the first to demonstrate a dysregulated proportion of ­CD19+IgD+CD27+ non-class-switched memory B cells and ­CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

Background: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched ­CD19+IgD−CD27+ on-class-switched ­CD19+IgD+CD27+ memory B cell subsets and ­CD19 + CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. Methods: This cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. Results: The frequency of ­­CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both ­CD19+IgD−CD27+ class-switched and ­­CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of ­CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. Conclusion This study is the first to demonstrate a dysregulated proportion of ­CD19+IgD+CD27+ non-class-switched memory B cells and ­CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

Background: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched ­CD19+IgD−CD27+ on-class-switched ­CD19+IgD+CD27+ memory B cell subsets and ­CD19 + CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. Methods: This cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. Results: The frequency of ­­CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both ­CD19+IgD−CD27+ class-switched and ­­CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of ­CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. Conclusion This study is the first to demonstrate a dysregulated proportion of ­CD19+IgD+CD27+ non-class-switched memory B cells and ­CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.