Molecular variability of FLT3/ITD mutants and their impact on the differentiation program of 32D cells: implications for the biological properties of AML blasts.
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.
Pekova
Sona
S
Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague, Czech Republic. sona.pekova@homolka.cz
Ivanek
Robert
R
Dvorak
Michal
M
Rueggeberg
Sabrina
S
Leicht
Stefan
S
Li
Xinping
X
Franz
Thomas
T
Kozak
Tomas
T
Vrba
Jiri
J
Koza
Vladimir
V
Karas
Michal
M
Schwarz
Jiri
J
Cetkovsky
Petr
P
Prucha
Miroslav
M
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*
C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3