1.
PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy.
Cicconi, L, Divona, M, Ciardi, C, Ottone, T, Ferrantini, A, Lavorgna, S, Alfonso, V, Paoloni, F, Piciocchi, A, Avvisati, G, et al
Leukemia. 2016;(10):1987-1992
Abstract
The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.
2.
Postprandial lipaemia induces an acute decrease of insulin sensitivity in healthy men independently of plasma NEFA levels.
Pedrini, MT, Niederwanger, A, Kranebitter, M, Tautermann, C, Ciardi, C, Tatarczyk, T, Patsch, JR
Diabetologia. 2006;(7):1612-8
Abstract
AIMS/HYPOTHESIS Typical Western diets cause postprandial lipaemia for 18 h per day. We tested the hypothesis that postprandial lipaemia decreases insulin sensitivity. SUBJECTS, MATERIALS AND METHODS Employing a randomised crossover design, we administered two types of virtually isocaloric meals to ten healthy volunteers on two separate occasions. The meals (Meals 1 and 2) were both designed to produce a rise in triglycerides, but only Meal 1 generated a rise in NEFA, too. Insulin sensitivity, as quantified by an IVGTT with minimal model analysis, was calculated postabsorptively at 08.00 h and postprandially at 13.00 h, i.e. 3 h after meal ingestion. RESULTS Triglycerides rose from 0.91+/-0.31 mmol/l postabsorptively to 2.08+/-0.70 mmol/l postprandially with Meal 1 (p=0.005) and from 0.92+/-0.41 to 1.71+/-0.79 mmol/l with Meal 2 (p=0.005). Neither the triglyceride levels at 13.00 h, nor the post-meal AUCs for triglycerides were statistically different between Meal 1 and Meal 2. NEFA rose from 0.44+/-0.17 mmol/l postabsorptively to 0.69+/-0.16 mmol/l postprandially with Meal 1 (p=0.005) and showed no significant change with Meal 2 (0.46+/-0.31 mmol/l postabsorptively vs 0.36+/-0.32 mmol/l postprandially, p=0.09). Both the NEFA level at 13.00 h and the post-meal AUC for NEFA were significantly higher after Meal 1 than Meal 2. Compared with the postabsorptive state, insulin sensitivity decreased postprandially after each of the two meals to a comparable degree (Meal 1: -53%, p=0.02; Meal 2: -45%, p=0.005). CONCLUSIONS/INTERPRETATION Our study reveals a drop in insulin sensitivity during postprandial lipaemia and strongly suggests that decreased insulin sensitivity is brought about by elevated plasma levels of triglyceride-rich lipoproteins independently of plasma NEFA levels.