title: Molecular variability of FLT3/ITD mutants and their impact on the differentiation program of 32D cells: implications for the biological properties of AML blasts.
abstract: FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with internal tandem duplications (ITDs) accounting for up to 30% of its mutations. To analyze the impact of individual ITDs on the expression profile of immature myeloid cells, we have established 32D cell lines expressing nine different FLT3/ITDs isolated from AML patients and subjected them to whole genome expression profiling and 2DE/LC/MS proteomics. Our data indicate that in comparison to the controls, FLT3/ITD-positive 32D cells exhibit less mature expression profiles resembling early hematopoietic progenitors. Moreover, our results suggest that there exist biological differences among individual ITD variants.
authors.affiliation: Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague, Czech Republic. sona.pekova@homolka.cz
authors.forename: Sona
authors.initials: S
authors.lastname: Pekova
authors.forename: Robert
authors.initials: R
authors.lastname: Ivanek
authors.forename: Michal
authors.initials: M
authors.lastname: Dvorak
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rueggeberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Leicht
authors.forename: Xinping
authors.initials: X
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozak
authors.forename: Jiri
authors.initials: J
authors.lastname: Vrba
authors.forename: Vladimir
authors.initials: V
authors.lastname: Koza
authors.forename: Michal
authors.initials: M
authors.lastname: Karas
authors.forename: Jiri
authors.initials: J
authors.lastname: Schwarz
authors.forename: Petr
authors.initials: P
authors.lastname: Cetkovsky
authors.forename: Miroslav
authors.initials: M
authors.lastname: Prucha
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001752:Blast Crisis / Q000235:genetics* / Q000473:pathology*; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005091:Exons; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020080:Tandem Repeat Sequences / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3