Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

EVI1 abrogates interferon-alpha response by selectively blocking PML induction.

Silvia Buonamici1, Donglan Li, Fady M Mikhail

  • 1Department of Pathology and Cancer Center, University of Illinois, Chicago, Illinois 60607, USA.

The Journal of Biological Chemistry
|November 3, 2004
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

MPRIP::PDGFRB fusion identified in a male patient with a myeloid/lymphoid neoplasm with eosinophilia.

Annals of hematology·2026
Same author

Case Report: <i>KMT2A</i> amplification in two adult patients with B-cell acute lymphoblastic leukemia.

Frontiers in oncology·2026
Same author

Validation of the 2025 IMS/IMWG risk classification in patients with newly diagnosed multiple myeloma treated with quadruplets and autologous stem cell transplant.

British journal of haematology·2026
Same author

Distinct trajectory of measurable residual disease in t(11;14) myeloma treated with quadruplet therapy.

Blood·2026
Same author

Long-read sequencing of single cell-derived melanoma subclones reveals divergent and parallel genomic and epigenomic evolutionary trajectories.

bioRxiv : the preprint server for biology·2025
Same author

Transitory Schwann Cell Precursor and hybrid states underpin melanoma therapy resistance and metastasis.

bioRxiv : the preprint server for biology·2025
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
Same journal

Introduction to the Thematic Review Series on Intracellular Protein Degradation. The ubiquitous biology of intracellular protein degradation: a tribute to Alfred L. ("Fred") Goldberg.

The Journal of biological chemistry·2026
Same journal

Correction: Aromatic residue-rich amino-terminal segments of temporin L self-assemble into collagen-mimetic peptides with cell-adhesion properties.

The Journal of biological chemistry·2026
Same journal

YhbO is a DJ-1 family glyoxalase and α-oxoaldehyde hydratase that confers resistance to reactive carbonyl stress (112).

The Journal of biological chemistry·2026
Same journal

ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.

The Journal of biological chemistry·2026
Same journal

PAX8 controls proximal tubule epithelial identity and stress response through epigenetic modification of distal regulatory elements.

The Journal of biological chemistry·2026
See all related articles

The oncogene EVI1 blocks the anti-cancer effects of Interferon-alpha (IFN-alpha) by inhibiting the tumor suppressor PML. This mechanism allows cancer cells to evade the immune response and promote leukemia growth.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • EVI1 is an oncogene implicated in myeloid leukemias, impairing hematopoietic cell proliferation, differentiation, and apoptosis.
  • Interferon-alpha (IFN-alpha) is a cytokine used to treat neoplastic disorders, including chronic myeloid leukemia, by controlling immune responses and tissue expansion.

Purpose of the Study:

  • To investigate how EVI1 influences the cellular response to IFN-alpha in hematopoietic progenitors.
  • To elucidate the molecular mechanisms by which EVI1 confers resistance to IFN-alpha.

Main Methods:

  • Studies were conducted in murine hematopoietic progenitors.
  • Assessed the effects of EVI1 expression on IFN-alpha-mediated antiproliferative and apoptotic pathways.
  • Investigated the impact of EVI1 on JAK/STAT signaling and IFN-responsive gene activation, specifically focusing on the tumor suppressor PML.

Related Experiment Videos

  • Utilized reporter gene assays and examined the role of Interferon-Stimulated Response Element (ISRE) position within the PML gene.

    • Main Results:

    • EVI1 expression completely abrogated the antiproliferative and apoptotic effects of IFN-alpha in hematopoietic progenitors.
    • EVI1 did not repress JAK/STAT signaling but prolonged STAT1 phosphorylation and IFN-dependent reporter gene activation.
    • EVI1 specifically repressed IFN-dependent induction of the tumor suppressor PML and blocked PML-activated apoptotic pathways.
    • The position of the ISRE within the first exon of PML was critical for blocking IFN-alpha induction; relocation restored IFN response in the presence of EVI1.

    Conclusions:

    • EVI1 confers resistance to IFN-alpha by specifically inhibiting PML induction and downstream apoptosis.
    • Stabilized STAT1 phosphorylation and prolonged binding to the PML first exon may impair PML transcription, leading to loss of IFN response.
    • This study reveals a novel oncogenic mechanism for evading cytokine-mediated growth control in cancer.