Publications

The diagnosis and risk stratification of acute myeloid leukemia (AML) primarily rely on morphologic analysis and assessment of karyotype by chromosome banding analysis. For decades, standard AML induction therapy has utilized the combination of anthracyclines and cytarabine. Despite the use of postremission therapy, less than half of patients with AML will be cured of their disease. Allogeneic hematopoietic stem cell transplantation combines cytoreductive chemotherapy with adoptive immunotherapy and may cure patients who fail chemotherapy alone. Recent advances in next-generation sequencing have yielded important insights into the molecular landscape of AML with normal karyotype. Integrated prognostic models incorporating somatic mutation analyses may outperform prediction based on conventional clinical and cytogenetic factors alone. We review the evolution of risk profiling of AML from the cytogenetic to molecular era and describe the implications for AML diagnosis and postremission therapy.

OBJECTIVE

Elevated levels of serum leptin are associated with increased adiposity and production of pro-inflammatory cytokines. Both cytokines and body adiposity have been shown to predict cardiovascular events and mortality. The primary objective of the present study is to explore the associations between serum leptin and all-cause mortality and mortality from cardiovascular disease (CVD) over a span of 10 years, controlling for body adiposity and proinflammatory cytokines.

METHODS

The Health, Aging and Body Composition (Health ABC) study is a prospective cohort of 3,075 older adults aged 70 to 79 years. This analysis includes 2,919 men and women with complete serum leptin and vital status data. Data on all-cause mortality and incident cardiovascular events (including Coronary Heart Disease and Congestive Heart Failure) were collected over 10 years of follow-up (mean 8.4 years).

RESULTS

Women with leptin in quartile 2 and 3 were at lower risk of all-cause mortality, and those with leptin in quartile 2 were at lower risk of mortality from CVD as compared to women with lowest leptin values when adjusted for age, race, site, years of education, alcohol use, smoking, and physical activity. When these associations were additionally adjusted for body fat, C-reactive protein and pro-inflammatory cytokines, women with leptin values in quartile 3 were at lower risk of all-cause mortality and women with leptin in quartile 2 and 3 were at lower risk of mortality from CVD than women with lowest leptin values. These associations were not significant among men after adjusting for body fat and cytokines.

CONCLUSIONS

The present study suggests that moderately elevated concentrations of serum leptin are independently associated with lower risk of all-cause mortality and CVD-related mortality among older women. Among men, serum leptin is not associated with reduced risk of all-cause and CVD mortality after controlling for body fat and cytokines.