Generation of a H9 Clonal Cell Line With Inducible Expression of NUP98-KDM5A Fusion Gene in the AAVS1 Safe Harbor Locus

Joan Domingo-Reinés; Gonzalo Martínez-Navajas; Rosa Montes; Mar Lamolda; Iris Simón; Julio Castaño; Rosa Ríos-Pelegrina; Javier Luis Lopez-Hidalgo; Raimundo García Del Moral; Juan A Marchal; Pedro J Real; Verónica Ramos-Mejía

doi:10.3389/fcell.2022.846092

Generation of a H9 Clonal Cell Line With Inducible Expression of NUP98-KDM5A Fusion Gene in the AAVS1 Safe Harbor Locus

Front Cell Dev Biol. 2022 Jun 1:10:846092. doi: 10.3389/fcell.2022.846092. eCollection 2022.

Authors

Joan Domingo-Reinés¹, Gonzalo Martínez-Navajas^{1

2}, Rosa Montes^{1

3}, Mar Lamolda¹, Iris Simón^{1

2}, Julio Castaño⁴, Rosa Ríos-Pelegrina^{5

6}, Javier Luis Lopez-Hidalgo^{5

6}, Raimundo García Del Moral^{5

6}, Juan A Marchal^{6

7

8

9}, Pedro J Real^{1

2

6}, Verónica Ramos-Mejía¹

Affiliations

¹ GENYO, Centre for Genomics and Oncological Research Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain.
² Faculty of Science, Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain.
³ Faculty of Sciences, Department of Cell Biology, University of Granada, Granada, Spain.
⁴ Advanced Cell Therapy Service, Banc de Sang I Teixits, Edifici Dr. Frederic Duran I Jordà, Barcelona, Spain.
⁵ Unidad de Anatomía Patológica, Hospital Universitario Clínico San Cecilio, Granada, Spain.
⁶ Instituto de Investigación Biosanitaria Ibs.GRANADA, Granada, Spain.
⁷ Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada, Spain.
⁸ Faculty of Medicine, Department of Human Anatomy and Embryology, University of Granada, Granada, Spain.
⁹ Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Granada, Spain.

Abstract

Pediatric acute myeloid leukemia (AML) is a rare and heterogeneous disease that remains the major cause of mortality in children with leukemia. To improve the outcome of pediatric AML we need to gain knowledge on the biological bases of this disease. NUP98-KDM5A (NK5A) fusion protein is present in a particular subgroup of young pediatric patients with poor outcome. We report the generation and characterization of human Embryonic Stem Cell (hESC) clonal lines with inducible expression of NK5A. Temporal control of NK5A expression during hematopoietic differentiation from hESC will be critical for elucidating its participation during the leukemogenic process.

Keywords: acute myeliod leukemia; disease model; hematopoieisis; human stem cell; pediatric.