Sharing and Helping: Regularity and Characteristics of Pathogenesis of a Widely Used Transgene Initiated Murine Acute Promyelocytic Leukemia Model

Stem Cells Dev. 2021 Jan 1;30(1):39-48. doi: 10.1089/scd.2020.0125. Epub 2020 Dec 15.

Abstract

A transgenic acute promyelocytic leukemia (APL) murine model established by Michael Bishop by cloning a human PML-RARα cDNA into the hMRP8 expression cassette has been widely used in the all-trans retinoid acid and arsenic preparations for the research of APL. However, in the existing literature, the data of regularity and characteristics of the pathogenesis of this model were still missing, which hinder the development of many studies, especially application of new technologies such as single-cell sequencing. Therefore, in this article, we have made up this part of the missing data using an improved APL murine model. We clarified the effects of different inoculation doses on the onset time, latency, morbidity, life span, and proportion of APL cells in peripheral blood (PB), spleen, bone marrow, and so on. The relationship between the proportion of APL cells in the bone marrow, spleen, and PB and organ histological changes was also revealed. These results were a supplement and refinement of this APL model. It would add to the knowledge base of the field and aid in ensuring that accurate models are used for directed interventions. It also provides a great convenience for the researchers who will carry out similar research.

Keywords: PML-RARα-GFP; acute promyelocytic leukemia; murine model; pathogenesis; regularity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Disease Models, Animal*
  • Flow Cytometry / methods
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Leukemia, Promyelocytic, Acute / blood
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / pathology
  • Male
  • Mice, Transgenic
  • Oncogene Proteins, Fusion / genetics*
  • Spleen / metabolism
  • Survival Analysis
  • Time Factors
  • Transgenes / genetics*

Substances

  • Oncogene Proteins, Fusion
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein