ICGP awardees strengthen geriatric psychiatry. The role of ICGP and of the journal

摘要

We aimed at developing novel assays for Loss of Heterozygosity (LOH) detection on 13q as a substitute for FLT3-ITD analysis to identify acute myeloid leukemia (AML) patients with high risk of shorter survival. To this aim, we first analyzed a selected cohort of 185 patients with (n=138) or without (n=47) FLT3-ITD by short tandem repeat (STR) analysis for 13q LOH. In 46 of 138 FLT3-ITD positive cases, a FLT3-ITD/FLT3wt ratio of ≥1 was measured indicating LOH. Applying analysis with a combination of five different STR markers, a threshold of an STR allelic ratio of >65% allows the identification of LOH in 40/46 (87%) samples. Survival analysis revealed significantly inferior outcome in patients with LOH as detected by STR analysis (event free survival (EFS): no LOH: 13.3 months versus LOH: 4.5 months, p<0.001; overall survival (OS): no LOH: 35.8 months versus LOH: 9.7 months, p=0.001). In multivariate Cox regression analysis, 13q LOH was found to be an independent adverse parameter for EFS and OS (p=0.003 and p<0.001, respectively) besides age and white blood cell count. Thus, the prognostic impact of 13q LOH is nearly identical to the one of FLT3-ITD/FLT3wt load of ≥1 and thus is a feasible alternative to identify respective patients with high risk AML. In a second approach, a cohort of 91 patients was subjected to a proof-of-principle study of applying single nucleotide polymorphism analysis by next generation amplicon sequencing for detection of LOH. 53/91 cases had LOH and 50 were identified with this new method resulting in a positive detection rate of 94.3%.