Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis
Jaclyn Andricovich, … , Adlen Foudi, Alexandros Tzatsos
Jaclyn Andricovich, … , Adlen Foudi, Alexandros Tzatsos
Published January 25, 2016
Citation Information: J Clin Invest. 2016;126(3):905-920. https://doi.org/10.1172/JCI84014.
View: Text | PDF
Research Article Hematology Article has an altmetric score of 5

Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis

  • Text
  • PDF
Abstract

The development of the hematopoietic system is a dynamic process that is controlled by the interplay between transcriptional and epigenetic networks to determine cellular identity. These networks are critical for lineage specification and are frequently dysregulated in leukemias. Here, we identified histone demethylase KDM2B as a critical regulator of definitive hematopoiesis and lineage commitment of murine hematopoietic stem and progenitor cells (HSPCs). RNA sequencing of Kdm2b-null HSPCs and genome-wide ChIP studies in human leukemias revealed that KDM2B cooperates with polycomb and trithorax complexes to regulate differentiation, lineage choice, cytokine signaling, and cell cycle. Furthermore, we demonstrated that KDM2B exhibits a dichotomous role in hematopoietic malignancies. Specifically, we determined that KDM2B maintains lymphoid leukemias, but restrains RAS-driven myeloid transformation. Our study reveals that KDM2B is an important mediator of hematopoietic cell development and has opposing roles in tumor progression that are dependent on cellular context.

Authors

Jaclyn Andricovich, Yan Kai, Weiqun Peng, Adlen Foudi, Alexandros Tzatsos

×

Figure 6

Prooncogenic role of KDM2B in lymphoid malignancies.

Options: View larger image (or click on image) Download as PowerPoint
Prooncogenic role of KDM2B in lymphoid malignancies.
(A) Meta-analysis o...
(A) Meta-analysis of KDM2B expression in 159 human cell lines established from leukemias, lymphomas, and MM obtained from CCLE. MCL, mantle cell lymphoma; DLBCL, diffuse large B cell lymphoma; BL, Burkitt’s lymphoma; NHL, non-Hodgkin’s lymphomas. (B) Percentage growth inhibition of B-ALL (SUP-B15 and REH), T-ALL (CCRF-CEM, JURKAT, ALL-SIL, HPB-ALL, LOUCY, DND41, and K3P), CML (K562), AML (THP1), and MM cell lines 7 days after KD of KDM2B. Results are mean ± SEM. (C) The indicated cell lines were infected with lentiviruses to KD KDM2B. Left: Western blot shows successful KD of the endogenous protein. Middle and right: 1 × 106 of those cells were injected in NSG mice via tail vein (n = 3 per group). After 3 months, mice were euthanized for histological analysis. H&E staining of lung sections shows reduced metastasis in mice that received cells treated with shKDM2B. Bar graph shows the average area of lung nodules. Asterisk indicates metastatic nodule. Scale bars: 200 μm. (D) Indicated cell lines were infected with lentiviruses to KD KDM2B. RNA was isolated and the gene-expression profile was obtained using the PrimeView microarray (Affymetrix). Bar graph shows IPA of the differentially expressed genes (P < 0.05 and fold change > 1.5). The x axis (log scale) corresponds to the binomial raw P values. (E) Ingenuity regulator analysis (see Methods) in JURKAT cells treated with shKDM2B. Regulators with z scores greater than 2 and P overlap values of less than 0.01 are shown.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 4 X users
On 1 Facebook pages
Referenced in 1 Wikipedia pages
72 readers on Mendeley
See more details