Related Experiment Video
Updated: Jul 7, 2026
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow
T Hara1, M Schwieger, R Kazama
1Stem Cell Project Group, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan. thara@rinshoken.or.jp
Abstract:
Identifying genetic pathways that cooperate in leukemogenesis facilitates our understanding of the molecular mechanisms at play. Interferon consensus sequence-binding protein (ICSBP) is a tumor suppressor, whose downregulation cooperates with BCR-ABL and NUP98-TOP1 gene products to accelerate leukemia induction in mouse models. Similarly, Meis1 synergizes with HoxA9 or NUP98-HOX (but not NUP98-TOP1) fusion genes to promote the early onset of leukemia. To investigate whether Icsbp deficiency interacts with Meis1 or its family member Meis3, we transplanted Icsbp(-/-) bone marrow (BM) cells after transduction with Meis1 or Meis3 retroviral vectors. Here, we show that enforced expression of Meis1 or Meis3 in Icsbp(-/-) BM cells induces a fatal, invasive myeloproliferative disease. Secondary mutations, such as activation of Mn1, led to the progression to acute myeloid leukemia in a few mice. Interestingly, expression of endogenous Meis1 and Meis3 mRNAs was repressed in the granulocytic progenitor population of Icsbp(-/-) mice. These results reveal a novel collaboration between Icsbp deficiency and Meis1/Meis3 in the acceleration of chronic myeloid leukemia-like disease.
Insights
Interferon consensus sequence-binding protein (ICSBP) deficiency accelerates leukemia when combined with Meis1 or Meis3. This collaboration leads to fatal myeloproliferative disease, revealing new insights into leukemia development.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Leukemogenesis involves complex genetic pathway cooperation.
- Interferon consensus sequence-binding protein (ICSBP) acts as a tumor suppressor, and its downregulation cooperates with oncogenes like BCR-ABL and NUP98-TOP1.
- Meis1 is known to synergize with specific fusion genes in promoting leukemia.
Purpose of the Study:
- To investigate the interaction between Icsbp deficiency and Meis1/Meis3 in leukemia development.
- To determine if Meis1 or Meis3 can cooperate with Icsbp deficiency to induce myeloproliferative disease.
Main Methods:
- Transplantation of Icsbp(-/-) bone marrow cells transduced with Meis1 or Meis3 retroviral vectors.
- Monitoring disease induction, progression, and secondary mutations in recipient mice.
- Analysis of endogenous Meis1 and Meis3 mRNA expression in specific cell populations.
Main Results:
- Enforced expression of Meis1 or Meis3 in Icsbp(-/-) bone marrow cells resulted in a fatal, invasive myeloproliferative disease.
- Secondary mutations, including Mn1 activation, contributed to the progression to acute myeloid leukemia in some cases.
- Endogenous Meis1 and Meis3 mRNA levels were found to be repressed in the granulocytic progenitor population of Icsbp(-/-) mice.
Conclusions:
- Icsbp deficiency collaborates with Meis1 and Meis3 to accelerate the development of chronic myeloid leukemia-like disease.
- This study uncovers a novel cooperative mechanism in leukemogenesis involving Icsbp and the Meis family.
- Understanding these interactions provides critical insights into the molecular basis of leukemia.
