Identification of a Chemoresistant Ã¢ÂÂOxidative State-LowÃ¢ÂÂ Leukemic Subpopulation in CD34+ Human Acute Myeloid LeukemiaIoannis Kotsianidis1*, Dimitra Kokkinou2, Elena K Siapati3, Paraskevi Miltiades1, Eleftheria Lamprianidou1, George Vassilopoulos3,4, Nicholas C Zoumpos1 and Alexandros Spyridonidis1
- *Corresponding Author:
- Ioannis Kotsianidis, MD, PhD
Department of Hematology
Democritus University of Thrace
Medical School, Dragana, Alexandroupolis 68100, Greece
E-mail: [email protected], [email protected]
Received date: August 04, 2014; Accepted date: September 23, 2014; Published date: September 25, 2014
Citation: Kotsianidis I, Kokkinou D, Siapati EK, Miltiades P, Lamprianidou E, et al. (2014) Identification of a Chemoresistant “Oxidative State-Low” Leukemic Subpopulation in CD34+ Human Acute Myeloid Leukemia. J Stem Cell Res Ther 4:235. doi:10.4172/2157-7633.1000235
Copyright: © 2014 Kotsianidis I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Both normal and malignant stem cells maintain lower levels of reactive oxygen species (ROS), but the redox state in acute myeloid leukemia (AML) has not been thoroughly characterized and the role of ROS in leukemogenesis is still unclear. Herein, we report the identification of a rare but distinct ROSlow subpopulation in primary CD34+ AML samples. Methods: We analysed the ROS state of a number of AML samples by flow cytometry using the redox-sensitive fluorescence dye 2’7;-dichlorodihydrofluorescein diacetate. We FACS-sorted the ROSlow cells and investigated their immunophenotype, in vivo engraftment potential as well as their ability to withstand chemotherapeutic treatment. Results: Compared to the total CD34+ cells the ROSlow subset contained significantly more CMP-like and less GMP-like progenitors and could establish leukemia in NOD/SCID mice. Additionally, ROSlow cells bore a chemoresistant phenotype as they were more quiescent than total CD34+ AML cells, and showed increased in vitro chemoresistance and markedly higher GM-CSF-induced phosphorylation of STAT5. Conclusions: Thus, the ROSlow subpopulation arises as a novel candidate for cell-specific therapeutic targeting in AML. Further studies will help to ascertain the exact role of the ROSlow subset in the pathobiology and clinical management of AML.