Growth factor-independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate.
Growth factor-independent 1B (GFI1B) is a transcription factor essential for the development and differentiation of erythroid and megakaryocytic lineages. We evaluated the GFI1B expression in erythroleukaemia and megakaryocytic leukaemia, as well as in patients with other subtypes of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), myelodysplastic syndrome (MDS), severe aplastic anaemia (SAA), myelofibrosis with myeloid metaplasia (MMM) and in healthy volunteers. GFI1B expression was increased at least threefold in patients with erythroleukaemia (P < 0.01 compared with controls) and megakaryocytic leukaemia (P < 0.05) as well as in their corresponding leukaemic cell lines HEL, K562, CMK and M-07e. Patients with undifferentiated or monocytic AML, ALL, MMM, MDS and CML had no significantly altered GFI1B expression, whereas GFI1B expression was decreased 10-fold in patients with SAA (P < 0.0001 compared with controls). Silencing GFI1B by transfection with small interfering RNA (siRNA) markedly reduced the proliferation rate in the leukaemic cell lines HEL, K562 and NB4 (P < 0.01). Concomitantly, we observed a two- to threefold increase in the apoptosis rate in these cells after transfection with siRNA towards GFI1B. Our data indicate that GFI1B plays a major role in AML-M6 and AML-M7 and qualifies as a target for anti-leukaemic strategies in these malignancies.
Elmaagacli
Ahmet H
AH
Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany. ahmet.elmaagacli@uni-essen.de
Koldehoff
Michael
M
Zakrzewski
Johannes L
JL
Steckel
Nina K
NK
Ottinger
Hellmut
H
Beelen
Dietrich W
DW
D000741:Anemia, Aplastic / Q000378:metabolism; D018952:Antigens, CD34 / Q000276:immunology; D017209:Apoptosis; D016022:Case-Control Studies; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000276:immunology / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D007947:Leukemia, Megakaryoblastic, Acute / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014162:Transfection / Q000379:methods; D020741:rho GTP-Binding Proteins / Q000235:genetics
D018952:Antigens, CD34; C111977:GFI1B protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D020741:rho GTP-Binding Proteins