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

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.

[1]  R. Meneveri,et al.  Prenatal Origin of Pediatric Leukemia: Lessons From Hematopoietic Development , 2021, Frontiers in Cell and Developmental Biology.

[2]  R. Stam,et al.  The clinical and biological characteristics of NUP98-KDM5A pediatric acute myeloid leukemia , 2020, Haematologica.

[3]  L. Espinosa,et al.  Development of embryonic and adult leukemia mouse models driven by MLL-ENL translocation. , 2020, Experimental hematology.

[4]  S. Raimondi,et al.  Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children’s Oncology Group , 2020, Haematologica.

[5]  M. Arcangeli,et al.  Ontogenic changes in hematopoietic hierarchy determine pediatric specificity and disease phenotype in fusion oncogene-driven myeloid leukemia. , 2019, Cancer discovery.

[6]  B. Wilhelm,et al.  Pediatric leukemia: Moving toward more accurate models. , 2019, Experimental hematology.

[7]  S. Strehl,et al.  Generation of CD34 Fluorescent Reporter Human Induced Pluripotent Stem Cells for Monitoring Hematopoietic Differentiation. , 2018, Stem cells and development.

[8]  M. Fraga,et al.  Generation and characterization of a human iPSC cell line expressing inducible Cas9 in the “safe harbor” AAVS1 locus , 2017, Stem cell research.

[9]  M. Kyba,et al.  MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome. , 2016, Cancer cell.

[10]  C. Zwaan,et al.  Pediatric AML: From Biology to Clinical Management , 2015, Journal of clinical medicine.

[11]  I. Slukvin Hematopoietic specification from human pluripotent stem cells: current advances and challenges toward de novo generation of hematopoietic stem cells. , 2013, Blood.

[12]  Dinshaw J. Patel,et al.  Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger , 2009, Nature.

[13]  M. Greaves,et al.  Leukemia in twins: lessons in natural history. , 2003, Blood.