Survival outcomes of CD34+CD38-LSCs and their expression of CD123 in adult AML patients

Asmaa M Zahran; Sanaa Shaker Aly; Amal Rayan; Omnia El-Badawy; Maged Abdel Fattah; Arwa Mohammed Ali; Hala M ElBadre; Helal F Hetta

doi:10.18632/oncotarget.26118

Survival outcomes of CD34⁺CD38^-LSCs and their expression of CD123 in adult AML patients

Oncotarget. 2018 Sep 25;9(75):34056-34065. doi: 10.18632/oncotarget.26118.

Authors

Asmaa M Zahran¹, Sanaa Shaker Aly², Amal Rayan³, Omnia El-Badawy⁴, Maged Abdel Fattah⁵, Arwa Mohammed Ali⁵, Hala M ElBadre⁶, Helal F Hetta⁴

Affiliations

¹ Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
² Clinical and Chemical Pathology Department, Faculty of Medicine, South Valley University, Qena, Egypt.
³ Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁴ Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁵ Medical Oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
⁶ Medical Biochemistry Department, Faculty of Medicine, Assiut University, Assiut, Egypt.

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⁺CD38^low/-CD123⁺ LSCs were 2.2± 0.4and 22.3± 2.6, respectively. The percentages of CD34⁺cells, CD34⁺CD38^- and CD34⁺CD38^low/-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.

Keywords: CD34+CD38-CD123+LSCs; CD34+CD38-LSCs; acute myeloid leukemia; disease free survival; overall survival.