Whole genome and transcriptome analysis of a novel AML cell line with a normal karyotype.
Acute myeloid leukemia (AML) occurs when hematopoietic progenitor cells acquire genetic defects blocking the regulation of normal growth and differentiation. Although recurrent translocations have been identified in AML, almost half of adult AML patients present with a normal karyotype (NK-AML). While cell line models exist to study AML, they frequently have abnormal/unstable karyotypes, while primary cells from NK-AML patients are difficult to maintain in vitro. Here we provide a thorough molecular characterization of a recently established cell line, CG-SH, which has normal cytogenetics, representing a useful new model for NK-AML. Using high-throughput DNA sequencing, we first defined the genetic background of this cell line. In addition to identifying potentially deleterious SNVs in genes relevant to AML, we also found insertions in both GATA2 and EZH2, two genes previously linked to AML. We further characterized the growth of this model system in vitro with a cytokine mix that promotes faster cell growth. We assessed gene expression changes after the addition of cytokines to the culture media and found differential expression in genes implicated in proliferation, apoptosis and differentiation. Our results provide a detailed molecular characterization of genetic defects in this cell line derived from an NK-AML patient.
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Laboratory for High Throughput Genomics, Montreal, QC, Canada; The Leucegene Project, Canada.
Géraldine
G
Gosse
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Laboratory for High Throughput Genomics, Montreal, QC, Canada.
Magalie
M
Celton
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Laboratory for High Throughput Genomics, Montreal, QC, Canada.
Vikie
V
Lamontagne
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Laboratory for High Throughput Genomics, Montreal, QC, Canada.
Audrey
A
Forest
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, Canada; Laboratory for High Throughput Genomics, Montreal, QC, Canada; The Leucegene Project, Canada. Electronic address: brian.wilhelm@umontreal.ca.
Brian T
BT
Wilhelm
D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D015894:Genome, Human; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D059467:Transcriptome
D017931:DNA Primers
Cytokines; EZH2; GATA2; NK-AML cell line; RNA-seq