Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells.

Leukemic-stem-cell-specific targeting may improve the survival of patients with acute myeloid leukemia (AML) by avoiding the ablative effects of standard regimens on normal hematopoiesis. Herein, we perform an unbiased screening of compounds targeting cell surface proteins and identify clinically used DPP4 inhibitors as strong suppressors of AML development in both murine AML models and primary human AML cells xenograft model. We find in retrovirus-induced AML mouse models that DPP4-deficient AML cell-transplanted mice exhibit delay and reversal of AML development, whereas deletion of DPP4 has no significant effect on normal hematopoiesis. DPP4 activates and sustains survival of AML stem cells that are critical for AML development in both human and animal models via binding with Src kinase and activation of nuclear factor κB (NF-κB) signaling. Thus, inhibition of DPP4 is a potential therapeutic strategy against AML development through suppression of survival and stemness of AML cells.

Outcomes of elective abdominal aortic aneurysm repair in the setting of malignancy.

OBJECTIVE: Elective abdominal aortic aneurysm (AAA) repair for patients with a diagnosis of cancer has remained controversial. In the present study, we evaluated the in-hospital outcomes for patients who had undergone AAA repair in the setting of a cancer diagnosis. METHODS: Inpatients (2008-2018) who had undergone elective AAA repair were selected from the Cerner Health Facts database using International Classification of Diseases, ninth and tenth revision, procedure codes. We used χ2 analysis and logistic regression models to evaluate the association of patient characteristics with the medical and vascular outcomes. RESULTS: A total of 8663 patients who had undergone AAA repair were identified (270 with a cancer diagnosis and 8393 without a cancer diagnosis). No significant demographic differences were found between the two groups, except that more patients with a cancer diagnosis had undergone endovascular aneurysm repair (EVAR) than open aneurysm repair (88.2% vs 82.1%; P = .01). Male reproductive organ (24.8%) and lung (24.4%) cancer were the most common cancer diagnoses in the cohort. The unadjusted analysis revealed that patients with a cancer diagnosis were more likely to require remedial EVAR (relative risk, 3.47; 95% confidence interval [CI], 1.18-10.2) or reoperation for bleeding, infection, or thrombosis (relative risk, 1.59; 95% CI, 1.09-2.32). Multivariable analysis demonstrated that, overall, patients with a cancer diagnosis were more likely to require a prolonged length of stay (odds ratio [OR], 2.2; 95% CI, 1.5-3.3) and to have developed respiratory failure (OR, 2.1; 95% CI, 1.3-3.4) or infection (OR, 1.7; 95% CI, 1.2-2.4). Similar point estimates were found for men with and without a cancer diagnosis. However, women with a cancer diagnosis had a greater odds of a prolonged length of stay compared with women without a cancer diagnosis (OR, 2.6; 95% CI, 1.2-5.6). EVAR in the presence of a cancer diagnosis was also significantly associated with poor outcomes. CONCLUSIONS: Elective AAA repair for patients with a cancer diagnosis was associated with a prolonged length of stay and the development of infection, respiratory failure, and vascular-specific complications during the inpatient hospitalization. Given that differences in outcomes stratified by gender and treatment modality have been shown for patients with a cancer diagnosis, careful patient selection is important and reinforces the finding that cancer exerts negative systemic postoperative effects even when treated or quiescent.