ABSTRACT
BACKGROUND AND AIM: Acute myeloid leukemia (AML) is one of the most common leukemias in adults. AML is generally regarded as a stem cell disease characterized by an accumulation of undifferentiated and functionally heterogeneous populations of cells, The aim of the present study was to identify leukemia stem cells in patients with AML and their correlations with treatment outcomes namely remission status, disease free survival, and overall survival. RESULTS: The mean percentages of CD34+CD38- and CD34+CD38low/-CD123+ LSCs were 2.2± 0.4and 22.3± 2.6, respectively. The percentages of CD34+cells, CD34+CD38- and CD34+CD38low/-CD123+ LSCs were significantly lower in AML patients with complete remission than those without complete response (P<0.001, P<0.004, P<0.001 respectively). The mean OS of all study patients was 20.03±1.2 months while the median OS was 21 months (95% CI=18.32-21.48). The mean DFS was 16.96±1.02 months and the median was 18 months (95% CI=8.9-11.4). DFS and OS were significantly higher among those who achieved CR than those without CR. In addition, there were significant negative effects of WBCs, CD34+cells, CD34+CD38- and CD34+CD38-CD123+LSCs on DFS and OS. PATIENTS AND METHODS: We investigated 30 patients with newly diagnosed AML; all patients underwent complete history taking, and thorough physical and clinical examination, complete blood count. Peripheral smears and bone marrow aspirates were also examined. Cytochemistry and immunophenotyping of leukemic cells were performed routinely in bone marrow using monoclonal antibodies. Flow cytometry was used to analyze leukemia stem cells and their expression of CD123. CONCLUSION: Our study elucidated that CD34+CD38-LSCs, with or without CD123+LSCs phenotype was present in a significant proportion of AML patients and it could be responsible for resistance to traditional treatments, and high percentage of MRD that was translated into significantly high number of non CR, poor DFS, and OS.
ABSTRACT
BACKGROUND: The bone marrow immunosuppressive microenvironment of AML patients sustains and modulates proliferation, survival and drug resistance of AML through deregulation of both innate and adaptive immune response. We aimed to investigate the level of Tregs, expression of Tim-3 on peripheral blood T cells, expression of CD200 in myeloid blasts in newly diagnosed AML patients with normal cytogenetics (AML-NC) and their prognostic impact. PATIENTS AND METHODS: This study included 40 patients with de novo AML-NC and 20 healthy controls. Flow-cytometry was used for detection of CD4+CD25+high FoxP3+ regulatory T cells, Tim-3 expression on peripheral blood T cells and CD200 expression on myeloid blasts. RESULTS: The percentages of CD4+CD25+high and CD4+CD25+high Foxp3+ Tregs were significantly increased in AML patients than controls. The levels of Tregs, Tim-3/CD4+, Tim-3/CD8+, CD200 and MFI of CD200 were significantly lower in responding patients than in those with persistent leukemia. Only high CD200 expression (> 50%) showed statistically significant worse OS with P< 0.04. CONCLUSION: The increased levels of Tregs, Tim-3 expression on peripheral blood T cells and CD200 expression in myeloid blast in AML patients could play a role in the development of AML. Analysis of these markers could serve as prognostic markers and might guide the therapy in AML patients in the future.
Subject(s)
Antigens, CD/metabolism , Hepatitis A Virus Cellular Receptor 2/metabolism , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/metabolism , T-Lymphocytes, Regulatory/metabolism , Adult , Biomarkers, Tumor , Bone Marrow/pathology , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Case-Control Studies , Cytogenetic Analysis , Female , Flow Cytometry , Gene Expression , Humans , Immunophenotyping , Leukemia, Myeloid, Acute/etiology , Leukemia, Myeloid, Acute/mortality , Lymphocyte Count , Male , Prognosis , T-Lymphocytes, Regulatory/immunologyABSTRACT
Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age- and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management.
