Journal article
Naïve T-cells in Myelodysplastic Syndrome Display Intrinsic Human Telomerase Reverse Transcriptase (hTERT) Deficiency
Leukemia, Vol.27(4), pp.897-906
10/17/2012
DOI: 10.1038/leu.2012.300
PMCID: PMC4346223
PMID: 23072779
Abstract
Telomeres are specialized structures providing chromosome integrity during cellular division along with protection against premature senescence and apoptosis. Accelerated telomere attrition in patients with Myelodysplastic Syndrome (MDS) occurs by an undefined mechanism. Although the MDS clone originates within the myeloid compartment, T-lymphocytes display repertoire contraction and loss of naïve T-cells. The replicative lifespan of T-cells is stringently regulated by telomerase activity. In MDS cases, we show that purified CD3+ T-cells have significantly shorter telomere length and reduced proliferative capacity upon stimulation compared to controls. To understand the mechanism, telomerase enzymatic activity and telomerase reverse transcriptase (
hTERT
) gene expression were compared in MDS cases (n=35) and healthy controls (n=42) within different T-cell compartments. Telomerase activity is greatest in naïve T-cells illustrating the importance of telomere repair in homeostatic repertoire regulation. Compared to healthy controls, MDS cases had lower telomerase induction (p<0.0001) that correlated with significantly lower
hTERT
mRNA (p<0.0001), independent of age and disease stratification.
hTERT
mRNA deficiency affected naïve but not memory T-cells, and telomere erosion in MDS occurred without evidence of an hTERT-promoter mutation, copy number variation or deletion. Telomerase insufficiency may undermine homeostatic control within the hematopoietic compartment and promote a change in the T-cell repertoire in MDS.
Details
- Title: Subtitle
- Naïve T-cells in Myelodysplastic Syndrome Display Intrinsic Human Telomerase Reverse Transcriptase (hTERT) Deficiency
- Creators
- Lili Yang - Tianjin Medical UniversityAdam Mailloux - University of South FloridaDana E. Rollison - University of South FloridaJeffrey S. Painter - University of South FloridaJaroslaw Maciejewski - Tianjin Medical UniversityRonald L. Paquette - University of California, Los AngelesThomas P. Loughran - Pennsylvania State UniversityKathy McGraw - University of South FloridaHideki Makishima - Tianjin Medical UniversityRangasudhagar Radhakrishnan - University of South FloridaSheng Wei - University of South FloridaXiubao Ren - Tianjin Medical University Cancer Institute and HospitalRami Komrokji - University of South FloridaAlan F. List - University of South FloridaP.K. Epling-Burnette - University of South Florida
- Resource Type
- Journal article
- Publication Details
- Leukemia, Vol.27(4), pp.897-906
- DOI
- 10.1038/leu.2012.300
- PMID
- 23072779
- PMCID
- PMC4346223
- ISSN
- 0887-6924
- eISSN
- 1476-5551
- Language
- English
- Date published
- 10/17/2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297423702771
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