Gene profiling of Graffi murine leukemia virus-induced lymphoid leukemias: identification of leukemia markers and Fmn2 as a potential oncogene.
The Graffi murine leukemia virus induces a large spectrum of leukemias in mice and thus provides a good model to compare the transcriptome of all types of leukemias. We analyzed the gene expression profiles of both T and B leukemias induced by the virus with DNA microarrays. Given that we considered that a 4-fold change in expression level was significant, 388 probe sets were associated to B, to T, or common to both leukemias. Several of them were not yet associated with lymphoid leukemia. We confirmed specific deregulation of Fmn2, Arntl2, Bfsp2, Gfra2, Gpm6a, and Gpm6b in B leukemia, of Nln, Fbln1, and Bmp7 in T leukemias, and of Etv5 in both leukemias. More importantly, we show that the mouse Fmn2 induced an anchorage-independent growth, a drastic modification in cell shape with a concomitant disruption of the actin cytoskeleton. Interestingly, we found that human FMN2 is overexpressed in approximately 95% of pre-B acute lymphoblastic leukemia with the highest expression levels in patients with a TEL/AML1 rearrangement. These results, surely related to the role of FMN2 in meiotic spindle maintenance, suggest its important role in leukemogenesis. Finally, we propose a new panel of genes potentially involved in T and/or B leukemias.
Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal, Montréal, QC, Canada.
Cyndia
C
Charfi
Véronique
V
Voisin
Louis-Charles
LC
Levros
Elsy
E
Edouard
Eric
E
Rassart
D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D000080865:Formins; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D009052:Leukemia Virus, Murine / Q000472:pathogenicity*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000378:metabolism; D015458:Leukemia, T-Cell / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D009857:Oncogenes; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D012192:Retroviridae Infections / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000235:genetics* / Q000378:metabolism; D000097764:ETS Translocation Variant 6 Protein
D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D000080865:Formins; D005819:Genetic Markers; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C549436:formin 2 protein, mouse