Abstract 3713: Higher numbers of cancer stem cells in the peripheral blood of children with B-ALL upon conventional chemotherapy

Abstract

Abstract Background: Acute lymphocytic leukemia (ALL) is biologically and clinically considered as a heterogeneous neoplasm of lymphoid progenitor cells in the bone marrow (BM). 15- 20 % of children with ALL who achieve an initial remission, will show relapse. One potential mechanism behind this relapse could be the emergence of cancer stem cells (CSCs) which are considered the driving force of tumourigenesis due to their ability of self-renewal as well as the emergence of immune regulatory cells including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg). Aim: the main aim of this study was to analyze the numbers of CSCs and correlate these numbers with the numbers of blast cells, MDSCs and Treg cells in children with B-ALL before and after induction of chemotherapy. Materials and Methods: CSCs were defined as CD45dimCD19+CD10+CD34+CD38-, MDSCs were defined as Lin-HLA-DR-CD33+CD11b+ and Treg cells were defined as CD4+CD25+CD127-. The frequencies of these cells were analyzed in the peripheral blood of B-ALL patients before (n= 10) and after (n= 10) induction of chemotherapy using flow cytometry. Results: Significant increases in the numbers of CSCs were shown in B-ALL patients after induction of chemotherapy as compared to newly diagnosed patients (7.6± 8.3 vs. 2.7± 2.4, P<0.05). The numbers of CSCs in ALL patents before and after induction of chemotherapy inversely correlated with the numbers of the blast cells. Additionally, the numbers of MDSCs and Treg cells were higher and lower, respectively, in patients after induction of chemotherapy as compared to before chemotherapy. Conclusion: Our results indicate that chemotherapy of B-ALL patients results in emergence of high numbers of CSCs and MDSCs which might be contributing, respectively, to tumor relapse and creation of systemic immune suppression. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger population of B-ALL patients at different treatment stages. Note: This abstract was not presented at the meeting. Citation Format: Mohamed L. Salem. Higher numbers of cancer stem cells in the peripheral blood of children with B-ALL upon conventional chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3713. doi:10.1158/1538-7445.AM2017-3713