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

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

Sjögren, Anna-Karin, 1980 (author): Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin,Wallenberg Laboratory,Institute of Medicine

Andersson, Karin, 1972 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberglaboratoriet,Institute of Medicine, Department of Internal Medicine,Wallenberg Laboratory

Wahlström, Annika, 1975 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin,Wallenberglaboratoriet,Institute of Medicine,Wallenberg Laboratory

Karlsson, Christin, 1956 (author): Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberg Laboratory,Institute of Medicine, Department of Internal Medicine

Swolin, Birgitta, 1939 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine

Bergö, Martin, 1970 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberglaboratoriet,Institute of Medicine, Department of Internal Medicine,Wallenberg Laboratory

(creator_code:org_t)

American Society of Hematology, 2009
2009
English.
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 114:17, s. 3629-32

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

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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