Hematopoiesis and leukemogenesis in mice expressing oncogenic NrasG12D from the endogenous locus

Abstract

NRAS is frequently mutated in hematologic malignancies. We generated Mx1-Cre, Lox-STOP-Lox (LSL) -

Oncogenic Ras scales the ALPS

“…8 The Mx1-Cre system has been used to induce a latent Nras LSL-G12D "knock-in" allele in mice resulting in both MPD and a polyclonal lymphoproliferative disorder (LPD). 9 Together, these studies-showing that endogenous K-Ras G12D and N-Ras G12D protein expression perturbs myeloid and lymphoid growth control-are consistent with the discovery of NRAS and KRAS mutations in patients with LPD.…”

“…In mice, genetic background strongly modulates the disease phenotype with LPD more prominent in the inbred C57Bl/6 strain. 8,9 Modifier loci could also exist in humans. Differences in the cell type in which the inciting mutations occur and/or in the nature of any cooperating mutations could determine whether a patient develops RALD, JMML, or another hematologic disease.…”

P53 deletion and NrasG12D cooperate for AML

“…Similarly, Nras G12D KI mice harbor a wide spectrum of myeloid diseases with a highly penetrant CMML in bone marrow transplantation assays. 2,3 However, none of these models develop AML, suggesting that other associated genetic or epigenetic events are necessary to induce a full-blown leukemia.…”

Deficiency of β Common Receptor Moderately Attenuates the Progression of Myeloproliferative Neoplasm in Nras/+ Mice

“…We and others previously reported that bone marrow cells from Nras G12D/ϩ mice form a significant number of colonies in the absence of cytokines (10,11). To determine whether the spontaneous colony formation of Nras G12D/ϩ cells depends on ␤c-mediated signaling, we isolated bone marrow cells from control, Nras G12D/ϩ , and Nras G12D/ϩ ; ␤c Ϫ/Ϫ mice and plated them in semi-solid medium in the absence of cytokines.…”