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Updated: Aug 6, 2026
Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
Published on: October 15, 2018
Comparative analysis of Tet2 catalytic-deficient and knockout bone marrow over time
Julio C Flores1, Kyoko Ito2, Cheng-Yen Huang1
1Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
Ten-eleven translocation 2 (TET2) impacts aging bone marrow hematopoiesis. Its functions affect myeloid and lymphoid cells differently, with catalytic-independent roles becoming more prominent in older Tet2 knockout models.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Ten-eleven translocation 2 (TET2) is a DNA dioxygenase crucial for gene regulation via DNA demethylation and chromatin modification.
- TET2 mutations are prevalent in hematologic malignancies, highlighting its importance in hematopoietic stem cell function.
- The age-dependent roles of TET2's catalytic and noncatalytic functions in hematopoiesis remain incompletely understood.
Purpose of the Study:
- To investigate the distinct impacts of TET2's catalytic and noncatalytic functions on hematopoiesis across different ages.
- To elucidate the molecular mechanisms underlying age-related changes in TET2-deficient hematopoietic stem cells.
Main Methods:
- Comparative bone marrow transplantation experiments using Tet2 catalytic mutant and knockout models at various ages (3, 6, 9, and 12 months).
- Transcriptomic analyses of Tet2-deficient hematopoietic stem and progenitor cells (Lin- cells).
Main Results:
- Tet2 catalytic mutant bone marrow consistently induced myeloid disorders regardless of age.
- Young Tet2 knockout bone marrow caused both lymphoid and myeloid diseases, while older Tet2 knockout bone marrow predominantly led to myeloid disorders with faster onset.
- Gene expression analysis revealed a shift from lymphoid to myeloid gene deregulation in Tet2 knockout cells with age, linked to hypermethylation of disease-associated genes.
Conclusions:
- Tet2's catalytic-dependent and -independent functions exert distinct influences on myeloid and lymphoid lineages during bone marrow aging.
- Age-related alterations in TET2 function contribute to the development of specific hematopoietic malignancies.
