Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice.

Cutts, Briony,1976Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberg Laboratory,Institute of Medicine, Department of Internal Medicine (author)

Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPDs) that do not progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase-activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, whether Nf1 deficiency would be redundant in K-RAS-induced MPD development or whether the 2 mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RAS(G12D) in mouse hematopoietic cells results in AML that was fatal in primary mice within 4 weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS.

Sjögren, Anna-Karin,1980Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin,Wallenberg Laboratory,Institute of Medicine(Swepub:gu)xsannz (author)
Andersson, Karin,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberglaboratoriet,Institute of Medicine, Department of Internal Medicine,Wallenberg Laboratory(Swepub:gu)xankar (author)
Wahlström, Annika,1975Gothenburg University,Göteborgs universitet,Institutionen för medicin,Wallenberglaboratoriet,Institute of Medicine,Wallenberg Laboratory(Swepub:gu)xsannj (author)
Karlsson, Christin,1956Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberg Laboratory,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xkarlc (author)
Swolin, Birgitta,1939Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xswobi (author)
Bergö, Martin,1970Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberglaboratoriet,Institute of Medicine, Department of Internal Medicine,Wallenberg Laboratory(Swepub:gu)xbmarl (author)
Göteborgs universitetWallenberglaboratoriet (creator_code:org_t)

By the author/editor: Cutts, Briony, 1 ...; Sjögren, Anna-Ka ...; Andersson, Karin ...; Wahlström, Annik ...; Karlsson, Christ ...; Swolin, Birgitta ...; show more...; Bergö, Martin, 1 ...; show less...

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