Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2019 Nov;104(11):2125-2128.
doi: 10.3324/haematol.2019.230029.

Standing at odds: mutated RAS and hematopoietic stem cells

Monica Nafria  1 , Constanze Bonifer  2
Affiliations
Editorial

Standing at odds: mutated RAS and hematopoietic stem cells

Monica Nafria et al. Haematologica. 2019 Nov.
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Co-expression of AML1-ETO and mutant RAS is incompatible with hematopoietic stem cell (HSC) maintenance. (A) In acute myeloid leukemia (AML) patients, HSC express AML1-ETO, but this is not sufficient to cause overt disease. AML leukemic blasts represent myeloid progenitors harboring the translocation that have undergone secondary oncogenic events, including mutations in signaling pathway genes such as the K-RASG12D/+. However, prior to Di Genua et al., the molecular explanation for the lack of mutations in signaling pathway genes in the pre-leukemic stem cells was unknown. HSC (purple cells), myeloid progenitors (purple cells with pink dots). (B) Di Genua et al. generated conditional murine knock-in models expressing human AML1-ETO and K-RAS(G12D) individually or in combination: Aml1ETO/+ (purple nuclei), K-RasG12D/+ (pink nuclei), and Aml1ETO/+ K-RasG12D/+(pink and dotted nuclei), respectively, and performed competitive transplantation assays to compare wild-type and transgenic stem cell activity and measure global gene expression as indicated. (C) Model of step-wise oncogenesis in t(8;21) patients: the presence of t(8;21) in HSC results in a quiescent phenotype. Acquisition of K-RAS(G12D) occurs at later stages and results in increased proliferation. However, the double oncogenic event is not sufficient to develop overt AML, and the nature and order of acquisition of additional oncogenic events remains unknown.
See this image and copyright information in PMC

Comment on

References

    1. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441. - PMC - PubMed
    1. Assi SA, Imperato MR, Coleman DJL, et al. Subtype-specific regulatory network rewiring in acute myeloid leukemia. Nat Genet. 2019;51(1):151–162. - PMC - PubMed
    1. Valk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004;350(16):1617–1628. - PubMed
    1. Szczepanski T, Harrison CJ, van Dongen JJ. Genetic aberrations in paediatric acute leukaemias and implications for management of patients. Lancet Oncol. 2010;11(9):880–889. - PubMed
    1. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016;374(23):2209–2221. - PMC - PubMed