ABSTRACT
Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries. While TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations, the lower threshold in mutation carriers was age-dependent, and adult mutation carriers often overlapped with the lowest decile of controls. The extent of telomere shortening correlated with the age at diagnosis as well as the short telomere syndrome phenotype. Extremely short TL caused bone marrow failure and immunodeficiency in children and young adults, while milder defects manifested as pulmonary fibrosis-emphysema in adults. We prospectively examined whether TL altered treatment decisions for newly diagnosed idiopathic bone marrow failure patients and found abnormally short TL enriched for patients with mutations in some inherited bone marrow failure genes, such as RUNX1, in addition to telomerase and telomere maintenance genes. The result was actionable, altering the choice of treatment regimen and/or hematopoietic stem cell donor in one-fourth of the cases (9 of 38, 24%). We conclude that TL measurement by flowFISH, when used for targeted clinical indications and in limited settings, can influence treatment decisions in ways that improve outcome.
Subject(s)
Pulmonary Emphysema/metabolism , Pulmonary Fibrosis/metabolism , Telomere Shortening , Telomere/metabolism , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Hospitals/statistics & numerical data , Humans , In Situ Hybridization, Fluorescence , Infant , Male , Middle Aged , Mutation , Pulmonary Emphysema/diagnosis , Pulmonary Emphysema/genetics , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/genetics , Telomerase/genetics , Telomerase/metabolism , Telomere/chemistry , Young AdultABSTRACT
This study determined the percentage of potential plasma donors who could donate plasma in the 3 allowable plasma volume limit categories as specified by the Food and Drug Administration (FDA), as well as the association of the body mass index (BMI) of these individuals with age, blood pressure, oral temperature, and pulse. Of 315 plasma donors analyzed, 107 (34.0%) weighed between 110 and 149 lbs (50.0-67.7 kg), 89 (28.2%) weighed between 150 and174 lbs (68.2-79.1 kg), and 119 (37.8%) weighed >175 lbs (79.5 kg), theoretically allowing collection of an additional 101.4 liters (16% more plasma) from both heavier categories based on FDA standards for plasma donor quantities. BMI was positively associated with age, mean arterial pressure (MAP), and pulse (Pearson's r = 0.36, 0.24, and 0.18, resp., P values <0.05), but not with oral temperature. Average BMI for females was higher than for males (+1.8, P = 0.01), and BMI for African Americans was higher than for White and Asian participants (+2.2 and +5.1, resp., Ps <0.05). A significant association was also found in the sex by race interaction with BMI (P = 0.0004). Follow-up analyses suggested a significant difference in BMI by sex among African Americans, higher BMI among African American females than Asian and White males, and higher BMI among White females than African American males (Ps <0.05).
