Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2018; 10(6): 57-65
Published online Jun 26, 2018. doi: 10.4252/wjsc.v10.i6.57
Murine models based on acute myeloid leukemia-initiating stem cells xenografting
Cristina Mambet, Mihaela Chivu-Economescu, Lilia Matei, Laura Georgiana Necula, Denisa Laura Dragu, Coralia Bleotu, Carmen Cristina Diaconu
Cristina Mambet, Mihaela Chivu-Economescu, Lilia Matei, Laura Georgiana Necula, Denisa Laura Dragu, Coralia Bleotu, Carmen Cristina Diaconu, Cellular and Molecular Pathology Department, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
Laura Georgiana Necula, Nicolae Cajal Institute, Titu Maiorescu University, Bucharest 040441, Romania
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by The project Competitiveness Operational Programme (COP) A1.1.4., No. P_37_798, Contract 149/26.10.2016 (MySMIS2014+: 106774).
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mihaela Chivu-Economescu, PhD, Research Assistant Professor, Research Scientist, Senior Researcher, Cellular and Molecular Pathology Department, Stefan S. Nicolau Institute of Virology, 285 Mihai Bravu Ave, Bucharest 030304, Romania. mihaela.chivu@gmail.com
Telephone: +40-21-3242590 Fax: +40-21-3242590
Received: April 28, 2018
Peer-review started: April 28, 2018
First decision: May 11, 2018
Revised: May 24, 2018
Accepted: June 8, 2018
Article in press: June 8, 2018
Published online: June 26, 2018
Processing time: 59 Days and 20.2 Hours
Abstract

Acute myeloid leukemia (AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells (LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop “humanized mice” that can support the engraftment of LSC. This present review is aiming to introduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.

Keywords: Acute myeloid leukemia; Leukemia-initiating stem cells; Antigen markers; Murine models; Xenografts

Core tip: The review is aiming to introduce the field of acute myeloid leukemia (AML) pathogenesis, the concept of leukemic stem cells, and also to present the current attempts to develop best AML animal models as means to investigate the factors responsible for leukemic transformation. Due to difficulties in engraftment of less aggressive AML samples, it is currently being attempted to develop humanized mice by introducing supporting human stromal cells as a source of proper cytokines, in a challenge to mimic an appropriate bone marrow niche able to support leukemic stem cells engraftment.