TARP as immunotherapeutic target in AML expressed in the LSC compartment

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Long non-coding RNAs in pluripotent stem cell biology

Pluripotent stem cells are defined by their unlimited self-renewal capacities and potential to differentiate into any cell lineage. Many crucial determinants for the induction and maintenance of this pluripotent state have been identified. Long non-coding RNAs have recently emerged as key regulators of pluripotent stem cells and have enhanced our understanding of their potential functions in tissue regeneration. This review provides an overview of recent important insights into the roles of long non-coding RNAs as regulators and markers of pluripotency

Conversion during laparoscopic aortobifemoral bypass: a failure?

OBJECTIVES: To study the impact of conversion on postoperative recovery, morbidity and mortality in laparoscopic aortobifemoral bypass surgery for aorto-iliac occlusive disease (AIOD). DESIGN: Retrospective analysis of a prospectively maintained database. METHODS: Between November 2002 and December 2006, 139 patients were treated for severe AIOD with a laparoscopic aortobifemoral bypass at one community and one university hospital. Demographic data, operative data, postoperative recovery data, morbidity and mortality were recorded and analysed according to a conversion and a non-conversion group. RESULTS: Conversion was needed in 13.7% of the patients. Morbidity was 16.5%-14.2% in the non-conversion group and 31.8% in the conversion group. Systemic morbidity was significantly higher in the conversion group (31.6% vs.10%; p=0.002), but only one patient had incomplete recovery; local morbidity was comparable in both groups (10.5% vs. 5.8%; p=0.337). Mortality rate was 2.2%. CONCLUSION: Laparoscopic aortobifemoral bypass surgery is a safe procedure for the treatment of AIOD. The outcome of patients after conversion is not affected in the way that it could be an impediment to start a laparoscopic procedure. Conversion in time is a safe way to overcome the learning curve.status: publishe

TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment

Immunotherapeutic strategies targeting the rare leukemic stem cell compartment might provide salvage to the high relapse rates currently observed in acute myeloid leukemia (AML). We applied gene expression profiling for comparison of leukemic blasts and leukemic stem cells with their normal counterparts. Here, we show that the T-cell receptor ? chain alternate reading frame protein (TARP) is over-expressed in de novo pediatric (n=13) and adult (n=17) AML sorted leukemic stem cells and blasts compared to hematopoietic stem cells and normal myeloblasts (15 healthy controls). Moreover, TARP expression was significantly associated with a Emslike tyrosine kinase receptor-3 internal tandem duplication in pediatric AML. TARP overexpression was confirmed in AML cell lines (n=9), and was found to be absent in B-cell acute lymphocytic leukemia (n=5) and chronic myeloid leukemia (n=1). Sequencing revealed that both a classical TARP transcript, as described in breast and prostate adenocarcinoma, and an AML-specific alternative TARP transcript, were present. Protein expression levels mostly matched transcript levels. TARP was shown to reside in the cytoplasmic compartment and showed sporadic endoplasmic reticulum co-localization. TARP-T-cell receptor engineered cytotoxic T-cells in vitro killed AML cell lines and patient leukemic cells co-expressing TARP and HLA-A*0201. In conclusion, TARP qualifies as a relevant target for immunotherapeutic T-cell therapy in AML