These findings suggest that the functional interplay between FLT3ITD and hTERT contributes to the AML pathogenesis and interferes with the efficacy of FLT3ITD-targeted therapy.
Simultaneous in vitro generation of CD8 and CD4 T cells specific to three universal tumor associated antigens of WT1, survivin and TERT and adoptive T cell transfer for the treatment of acute myeloid leukemia.
We developed a quantitative pyrosequencing-based methylation assay covering the TERT proximal promoter and a partial exon 1 (TERTpro/Ex1) region and tested both cell lines and primary leukaemia cells derived from AML and AML with preceding myelodysplastic syndrome (AML/MDS) patients (n = 43).
We screened variants in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) genes, and investigated the 3'-overhang length in bone marrow samples from 72 Chinese patients with AML (61 de novo, 11 secondary, excluding M3), aged 13-77.
Variants within the TERT gene have been associated with increased risk of haematological malignancies, including myelodysplastic syndrome and acute myeloid leukaemia as well as chronic lymphocytic leukaemia.
In six generations of a large family, a loss-of-function mutation in the telomerase enzyme gene TERT associated with severe telomere shortening and a range of hematologic manifestations, from macrocytosis to acute myeloid leukemia, with severe liver diseases marked by fibrosis and inflammation, and one case of idiopathic pulmonary fibrosis but not with autoimmune disorders.
We have now identified novel mutations in the telomerase RNA (TERC) or telomerase reverse transcriptase component (TERT) within 4 of 20 families presenting with familial MDS/AML.
To test the role of telomerase in acute myeloid leukemia (AML), we expressed the telomerase reverse transcriptase (hTERT) gene, a dominant-negative hTERT (DN-hTERT) (D868A, D869A) gene, or a gene encoding green fluorescence protein (GFP) in the leukemia cell line K562 and in primary AML cells from different patients, using retroviral vectors.