Lipoprotein(a) (Lp[a]) is an established predictor of cardiovascular risk but associations with secondary events are less certain, and data on understudied ethnic groups are scarce. This study aimed t Show more
Lipoprotein(a) (Lp[a]) is an established predictor of cardiovascular risk but associations with secondary events are less certain, and data on understudied ethnic groups are scarce. This study aimed to assess the association between Lp(a) and secondary events and explore variation in Lp(a) levels by ethnicity in first-time acute coronary syndrome (ACS) patients, to inform future risk prediction models. The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) is a longitudinal multi-centre cohort study of 1900 patients enrolled during their ACS admission. Baseline plasma Lp(a) concentrations were measured using an isoform-insensitive assay measured in nmol/L. The primary outcome was a composite of all-cause mortality or cardiovascular readmission, ascertained through national health datasets. Cox regression models were used to assess the association between Lp(a) levels and outcomes, adjusted for clinical risk factors. The mean age was 61 years, 20 % were female, and 73 % were European, 14 % Māori, 5 % Pacific peoples, 4 % Indian and 3 % other ethnicities. Of 1890 alive at discharge, 493 (26 %) experienced the primary outcome over a median follow-up of 4.9 years. Higher Lp(a) levels were associated with increased risk of secondary events. Compared to the lowest quartile (≤7 nmol/L), the adjusted hazard ratio for the highest quartile (>92 nmol/L) was 1.46 (95 %CI 1.12-1.89, p = 0.004). In this ACS cohort, Lp(a) concentrations varied by ethnicity, being highest amongst Indian participants (median 27 nmol/L) and lowest amongst Māori participants (median 12 nmol/L). Elevated Lp(a) concentrations are associated with secondary events following ACS. Further research is needed to define optimal thresholds for increased risk and explore ethnic-specific implications for secondary prevention. Show less
MLLT10 (previously called AF10) is a moderately common MLL fusion partner predominantly occurring in acute monoblastic leukemia (AML-M5). 10;11 rearrangements require at least three breaks in order to Show more
MLLT10 (previously called AF10) is a moderately common MLL fusion partner predominantly occurring in acute monoblastic leukemia (AML-M5). 10;11 rearrangements require at least three breaks in order to generate an in-frame MLL-MLLT10 fusion as a result of the opposite orientations of both genes on the respective chromosome arms. In this study, we describe a detailed molecular cytogenetic analysis of MLL-MLLT10 positive 10;11 rearrangements in two patients. We observed an as yet unreported chromosomal mechanism with at least four breakpoints, leading to MLL-MLLT10 gene fusion in a 24-year-old male. An inversion of 11q13-q23 with a breakpoint in the MLL gene was followed by an additional break 3' of MLL prior to insertion of the 11q segment into MLLT10. In a second patient, a 37-year-old male with AML-M5b, molecular cytogenetic analysis of an apparent 10;11 reciprocal translocation showed an intrachromosomal inversion of 3'MLLT10followed by a reciprocal translocation between 10p12 and 11q23. Review of the literature showed that all cases were the result of an inversion of either 10p or 11q followed by translocation 10p;11q or insertion of the inverted segment into MLLT10 or MLL. Show less