MN1 overexpression is an important step in the development of inv(16) AML.
The gene encoding the transcriptional co-activator MN1 is the target of the reciprocal chromosome translocation (12;22)(p13;q12) in some patients with acute myeloid leukemia (AML). In addition, expression array analysis showed that MN1 was overexpressed in AML specified by inv(16), in some AML overexpressing ecotropic viral integration 1 site (EVI1) and in some AML without karyotypic abnormalities. Here we describe that mice receiving transplants of bone marrow (BM) overexpressing MN1 rapidly developed myeloproliferative disease (MPD). This BM also generated myeloid cell lines in culture. By mimicking the situation in human inv(16) AML, forced coexpression of MN1 and Cbfbeta-SMMHC rapidly caused AML in mice. These findings identify MN1 as a highly effective hematopoietic oncogene and suggest that MN1 overexpression is an important cooperative event in human inv(16) AML.
Carella
C
C
Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN 38105-0318, USA.
Bonten
J
J
Sirma
S
S
Kranenburg
T A
TA
Terranova
S
S
Klein-Geltink
R
R
Shurtleff
S
S
Downing
J R
JR
Zwarthoff
E C
EC
Liu
P P
PP
Grosveld
G C
GC
D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009196:Myeloproliferative Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D015534:Trans-Activators; D014178:Translocation, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins
C095514:CBFbeta-MYH11 fusion protein; C501081:Mn1 protein, mouse; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins