Abstract

Murine erythroleukemia (MEL) cells are often employed as a model to dissect mechanisms of erythropoiesis and erythroleukemia in vitro. Here, an allograft model using MEL cells resulting in splenomegaly was established to develop a diagnostic model for isolation/quantification of metastatic cells, anti-cancer drug screening, and evaluation of the tumorigenic or metastatic potentials of molecules in vivo. In this animal model, circulating MEL cells from the blood stream were successfully isolated and quantified with an additional in vitro cultivation step. In terms of the molecular-pathological analysis, we were able to successfully evaluate the functional discrimination between methyl-CpG-binding domain 2 (Mbd2) and p66α in erythroid differentiation, and tumorigenic potential in spleen and blood stream of allograft model mice. In addition, we found that the number of circulating MEL cells in anti-cancer drug-treated mice was dose-dependently decreased. Our data demonstrate that the newly established allograft model is useful to dissect erythroleukemia pathologies and non-invasively provides valuable means for isolation of metastatic cells, screening of anti-cancer drugs, and evaluation of the tumorigenic potentials.

Highlights

  • Erythroleukemia is a subtype of acute myeloid leukemia (AML), accounting for 3~5% of AML cases

  • We found earlier that the Mi-2/nucleosome remodeling deacetylase (NuRD) chromatin remodeling complex (CRC) potentiates erythroid differentiation of proerythroblasts by regulating functions of the

  • Several issues in the development of animal models for cancer research have been encountered, such as different susceptibility of various mouse and rat strains to cancers, genetic diversions and technical variations in the animals, and polygenic predisposition in different strains controlled by multiple genetic loci [31,32,33,34,35,36,37,38]

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Summary

Introduction

Erythroleukemia is a subtype of acute myeloid leukemia (AML), accounting for 3~5% of AML cases. It is a neoplastic proliferation of erythroid and myeloid precursors of bone marrow hematopoietic stem cells [1]. It represents a phenotypically distinct form of AML characterized by unfavorable risk karyotype and disease features [2]. After a century of its descriptive history, many diagnostic, prognostic, and therapeutic implications related to this unique leukemia form remain uncertain. Cancers 2019, 11, 1707 disease and the simultaneous involvement of associated myeloid compartment have complicated the in vitro studies of human erythroleukemia cell lines.

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