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Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis

Yu Qian1, Jutatip Panaampon1, Bjoern Chapuy2

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Cell Reports
|July 10, 2026
PubMed

Insights

Dual-specificity phosphatase 2 (DUSP2) unexpectedly drives lymphoid malignancies by promoting cell cycle progression. Inhibiting DUSP2 may offer a novel therapeutic strategy for these cancers.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Dual-specificity phosphatase 2 (DUSP2) is a nuclear phosphatase primarily found in immune cells.
  • Its expression increases with immune cell stimulation and is linked to differentiation and function.
  • The role of DUSP2 in immune cell proliferation and hematologic cancers remains unclear.

Purpose of the Study:

  • To investigate the role of DUSP2 in immune cell proliferation and hematologic malignancies.
  • To elucidate the underlying mechanisms by which DUSP2 influences cell cycle progression and cancer development.

Main Methods:

  • Analysis of DUSP2 expression in human hematologic malignancies.
  • Gene silencing of DUSP2 in lymphoma cell lines.
  • Transgenic mouse models with altered DUSP2 expression.
  • Biochemical assays to determine DUSP2's interaction with cell cycle regulators.

Main Results:

  • DUSP2 is highly expressed in various human hematologic malignancies, including B-cell and T-cell lymphomas.
  • Reducing DUSP2 levels in lymphoma cells inhibits their growth and viability.
  • Elevated DUSP2 expression in mice enhances B-cell and T-cell proliferation and promotes malignant transformation.
  • DUSP2 activates CDK1 by recruiting CDC25 phosphatases, independent of its own catalytic activity, thus promoting cell cycle progression.

Conclusions:

  • DUSP2 plays an unexpected oncogenic role in lymphoid malignancies.
  • A structural motif in DUSP2, rather than its phosphatase activity, mediates cell cycle activation.
  • DUSP2 represents a potential therapeutic target for treating hematologic cancers.

Keywords:
CDC25CDK1CP: CancerCP: ImmunologyDUSP2, PAC-1cell cyclehematologic malignanciesimmune celllymphomagenesis

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