title: Generation of a MLL-AF9-specific stem cell model of acute monocytic leukemia.
abstract: Acute monocytic leukemia (AML-M5), a subtype of acute myeloid leukemia (AML), affects mostly young children and has poor prognosis. The mechanisms of treatment failure of AML-M5 are still unclear. In this study, we generated iPSC from THP-1 cells from a patient with AML-M5, using retroviruses encoding the pluripotency-associated genes (OCT3/4, SOX2, KLF4 and c-MYC). These AML-M5-derived iPSC showed features similar with those of human embryonic stem cells in terms of the morphology, gene expression, protein/antigen expression and differentiation capability. Parental-specific markers were down-regulated in these AML-M5-derived iPSCs. Expression of MLL-AF9 fusion gene (previously identified to be associated with pathogenesis of AML-M5) was observed in all iPSC clones as well as parental cells. We conclude that AML-M5-specific iPSC clones have been successfully developed. This disease model may provide a novel approach for future study of pathogenesis and therapeutic intervention of AML-M5.
authors.affiliation: a Faculty of Medicine and Health Sciences , Universiti Tunku Abdul Rahman , Kajang , Malaysia.
authors.forename: Men Yee
authors.initials: MY
authors.lastname: Chiew
authors.affiliation: a Faculty of Medicine and Health Sciences , Universiti Tunku Abdul Rahman , Kajang , Malaysia.
authors.forename: Nem Yun
authors.initials: NY
authors.lastname: Boo
authors.affiliation: b Research Laboratory , International Medical University , Bukit Jalil , Malaysia.
authors.forename: Kenny
authors.initials: K
authors.lastname: Voon
authors.affiliation: a Faculty of Medicine and Health Sciences , Universiti Tunku Abdul Rahman , Kajang , Malaysia.
authors.forename: Soon Keng
authors.initials: SK
authors.lastname: Cheong
authors.affiliation: a Faculty of Medicine and Health Sciences , Universiti Tunku Abdul Rahman , Kajang , Malaysia.
authors.forename: Pooi Pooi
authors.initials: PP
authors.lastname: Leong
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D065150:Cellular Reprogramming; D015870:Gene Expression; D020869:Gene Expression Profiling; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C474558:MLL-AF9 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein
keywords: Acute monocytic leukemia; MLL-AF9; acute myeloid leukemia; induced pluripotent stem cells