Body condition explains migratory performance of a long-distance migrant.

Body condition (i.e. relative mass after correcting for structural size) affects the behaviour of migrating birds, but how body condition affects migratory performance, timing and fitness is still largely unknown. Here, we studied the effects of relative body condition on individual departure decisions, wind selectivity, flight speed and timing of migration for a long-distance migratory shorebird, the red knot Calidris canutus rufa. By using automated VHF telemetry on a continental scale, we studied knots' migratory movements with unprecedented temporal resolution over a 3-year period. Knots with a higher relative body condition left the staging site later than birds in lower condition, yet still arrived earlier to their Arctic breeding grounds compared to knots in lower relative body condition. They accomplished this by selecting more favourable winds at departure, thereby flying faster and making shorter stops en route Individuals with a higher relative body condition in spring migrated south up to a month later than individuals in lower condition, suggesting that individuals in better condition were more likely to have bred successfully. Moreover, individuals with a lower relative body condition in spring had a lower probability of being detected in autumn, suggestive of increased mortality. The pressure to arrive early to the breeding grounds is considered to be an important constraint of migratory behaviour and this study highlights the important influence of body condition on migratory decisions, performance and potentially fitness of migrant birds.

Metal Levels in Shorebird Feathers and Blood During Migration Through Delaware Bay.

We investigated levels of arsenic mercury, lead, cadmium, and chromium in Red Knot (Calidris canutus), Semipalmated Sandpipers (Calidris pusilla), and Sanderling (Calidris alba) migrating through Delaware Bay, New Jersey to determine if contaminant levels are likely to be causing negative effects on the populations of these shorebirds, to compare among species, and to explore differences among individuals collected early and late during their migration stopover. We analyzed blood and feathers, both nonlethal ways of exploring contaminants in birds. Blood contaminant analysis provides a direct measure of recent dietary exposure, whereas feathers reflect body burden at the time of feather molt. We found some differences among species and between early and late samples. Levels of Hg and Pb were higher in Sanderling blood collected early (36.52 ± 8.45 and 145.00 ± 12.56 ng/g ww respectively) compared with later (16.21 ± 6.03 and 33.60 ± 4.05 ng/g ww respectively) during the migration stopover. Blood Pb levels of Sanderling in the early period were higher than those of the other two species (75.38 ± 15.52 ng/g ww in Red Knot and 42.39 ± 8.42 ng/g ww in Semipalmated Sandpipers). Semipalmated Sandpipers had lower blood As levels than the other two species (254.33 ± 40.15 and 512.00 ± 66.79 ng/g ww early and late respectively) but higher feather levels (914.01 ± 167.29 and 770.00 ± 116.21 ng/g dw early and late respectively), and their blood As was higher in the later sampling period compared with the early sampling period. Arsenic levels in shorebird tissues were relatively high and may reflect levels in horseshoe crab eggs, their primary diet item in Delaware Bay. In Red Knot, blood Cr levels were elevated in the later samples (572.17 ± 62.82 ng/g ww) compared to the early samples (382.81 ± 95.35 ng/g ww) and to the other species. The mean values of the metals analyzed were mostly below effect levels-the level that has a measurable negative impact-although relatively high As levels in Semipalmated Sandpiper feathers and some high levels of Pb need to be further explored.

Stakeholder contributions to assessment, monitoring, and conservation of threatened species: black skimmer and red knot as case studies.

Stakeholder contributions to conservation projects often occur during the problem formulation stage, yet the role of stakeholders throughout the process is seldom considered. We examine the diversity of state and federal agencies, conservation organizations, other non-governmental organizations, environmental justice communities, consultants, industry, and the general public in the conservation of red knot (Calidris canutus rufa) and black skimmer (Rynchops niger) in New Jersey. We suggest that (1) governmental agencies provide the legal, regulatory, and management framework, but it is often the universities, conservation organizations, consultants, and the public that conduct the research and perform activities that lead to increased research and conservation efforts; (2) departments within agencies may have conflicting mandates, making it difficult to resolve differences in actions; (3) there is often conflict among and within state agencies and conservation organizations about roles and priorities; and (4) the role of the public is critical to ongoing research and conservation efforts. Identification of all the relevant stakeholders is necessary to recognizing competing claims, identifying the threats, deciding how to manage the threats, and enhancing population viability. Conflicts occur even within an agency when one department oversees science and protection of populations and another oversees and fosters an industry (aquaculture or fisheries, or permits for off-road vehicles). Conflicts also occur between resource agencies, industry, and conservation organizations. Recognizing the different stakeholders and their mandates, and encouraging participation in the process, leads to a better understanding of the threats, risks, and possible solutions when conflicts arise. Tracking stakeholder viewpoints and actions can lead to increased involvement and conflict resolution.

Complexity of bioindicator selection for ecological, human, and cultural health: Chinook salmon and red knot as case studies.

There is considerable interest in developing bioindicators of ecological health that are also useful indicators for human health. Yet, human health assessment usually encompasses physical/chemical exposures and not cultural well-being. In this paper, we propose that bioindicators can be selected for all three purposes. We use Chinook or king salmon (Oncorhynchus tshawytscha) and red knot (Calidris canutus rufa, a sandpiper) as examples of indicators that can be used to assess human, ecological, and cultural health. Even so, selecting endpoints or metrics for each indicator species is complex and is explored in this paper. We suggest that there are several endpoint types to examine for a given species, including physical environment, environmental stressors, habitat, life history, demography, population counts, and cultural/societal aspects. Usually cultural endpoints are economic indicators (e.g., number of days fished, number of hunting licenses), rather than the importance of a fishing culture. Development of cultural/societal endpoints must include the perceptions of local communities, cultural groups, and tribal nations, as well as governmental and regulatory communities (although not usually so defined, the latter have cultures as well). Endpoint selection in this category is difficult because the underlying issues need to be identified and used to develop endpoints that tribes and stakeholders themselves see as reasonable surrogates of the qualities they value. We describe several endpoints for salmon and knots that can be used for ecological, human, and cultural/societal health.

Metals in tissues of migrant semipalmated sandpipers (Calidris pusilla) from Delaware Bay, New Jersey.

There is an abundance of field data on levels of metals for feathers in a variety of birds, but relatively few data for tissues, especially for migrant species from one location. In this paper we examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in muscle, liver, brain, fat and breast feathers from migrant semipalmated sandpipers (Calidris pusilla) collected from Delaware Bay, New Jersey. Our primary objectives were to (1) examine variation as a function of tissue, (2) determine the relationship of metal levels among tissues, and (3) determine the selenium:mercury molar ratio in different tissues since selenium is thought to protect against mercury toxicity. We were also interested in whether the large physiological changes that occur while shorebirds are on Delaware Bay (e.g. large weight gains in 2-3 weeks) affected metal levels, especially in the brain. There were significant differences among tissues for all metals. The brain had the lowest levels of arsenic and cadmium, and was tied for the lowest levels of all other metals except lead and selenium. Correlations among metals in tissues were varied, with mercury levels being positively correlated for muscle and brain, and for liver and breast feathers. Weights vary among individuals at the Delaware Bay stopover, as they arrive light, and gain weight prior to migration north. Bird weight and levels of arsenic, cadmium, and selenium in the brain were negatively correlated, while they were positively correlated for lead. There was no positive correlation for mercury in the brain as a function of body weight. The selenium:mercury molar ratio varied significantly among tissues, with brain (ratio of 141) and fat having the highest ratios, and liver and breast feathers having the lowest. In all cases, the ratio was above 21, suggesting the potential for amelioration of mercury toxicity.

Bioaccumulation of Some Metals and Metalloids in Laughing Gulls (Leucophaeus atricilla): Increases in Mercury and Decreases in Selenium from 2019 to 2022/2023.

The elements in blood normally reflect the levels in prey, indicating a recent exposure. Laughing gulls (Leucophaes atricilla) eat mainly horseshoe crab eggs (Limulus polyphemus) in the spring in Delaware Bay, New Jersey. The levels of arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg), and selenium (Se) in the blood of laughing gulls foraging on crab eggs were examined in Delaware Bay to provide information on a species that is normally a generalist, and to determine if the levels of these elements were similar in 2019 and 2022/2023, were intercorrelated, and were related to those in crab eggs. Hg increased from 2019 (136 ± 31 ng/g) to 2022/2023 (473 ± 75 ng/g), while Cd and Se decreased. There were some significant correlations among elements and a close relationship between the element levels in blood and those in crab eggs collected in the same month (except for As). The levels differed between laughing gulls and three species of shorebirds for As and Cd. The elements in the blood of gulls and shorebirds should be similar because they eat mainly the same eggs in the same places. A significant proportion of laughing gull blood samples had levels of Hg and Se that were above the levels associated with adverse effects, which requires further examination.

Annual survival of ruddy turnstones is not affected by natural infection with low pathogenicity avian influenza viruses.

The population of ruddy turnstones (Arenaria interpres morinella) that migrates through Delaware Bay has undergone severe declines in recent years, attributable to reduced availability of horseshoe crab (Limulus polyphemus) eggs at this critical spring migration stopover site. Concurrently, this population has experienced annual low pathogenicity avian influenza virus (AIV) epidemics at this same site. Using a prospective cohort study design with birds individually flagged during May-June 2006-2008, we evaluated resighting rates (a proxy for annual survival) between AIV-infected and uninfected birds at 1 yr after capture, testing, and measurement. Overall resighting rate was 46%, which varied by year and increased with relative mass of the bird when captured. Resighting rates were not different between AIV-infected and uninfected birds in any period. In multivariate analyses, infection status was also unrelated to resighting rate after controlling for year, day, state, sex, body size, mass index, or whether the bird was blood-sampled. Thus, apparent annual survival in ruddy turnstones was not reduced by AIV infection at this migratory stopover. However, it is unknown whether intestinal AIV infection might cause subtle reductions in weight gain which could negatively influence reproduction.

Influenza A Viruses in Ruddy Turnstones (Arenaria interpres); Connecting Wintering and Migratory Sites with an Ecological Hotspot at Delaware Bay.

Each May for over three decades, avian influenza A viruses (IAVs) have been isolated from shorebirds and gulls (order Charadriiformes) at Delaware Bay (DE Bay), USA, which is a critical stopover site for shorebirds on their spring migration to arctic breeding grounds. At DE Bay, most isolates have been recovered from ruddy turnstones (Arenaria interpres), but it is unknown if this species is involved in either the maintenance or movement of these viruses outside of this site. We collected and tested fecal samples from 2823 ruddy turnstones in Florida and Georgia in the southeastern United States during four winter/spring sample periods-2010, 2011, 2012, and 2013-and during the winters of 2014/2015 and 2015/2016. Twenty-five low pathogenicity IAVs were recovered representing five subtypes (H3N4, H3N8, H5N9, H6N1, and H12N2). Many of these subtypes matched those recovered at DE Bay during the previous year or that year's migratory cycle, suggesting that IAVs present on these southern wintering areas represent a source of virus introduction to DE Bay via migrating ruddy turnstones. Analyses of all IAV gene segments of H5N9 and H6N1 viruses recovered from ruddy turnstones at DE Bay during May 2012 and from the southeast during the spring of 2012 revealed a high level of genetic relatedness at the nucleotide level, suggesting that migrating ruddy turnstones move IAVs from wintering grounds to the DE Bay ecosystem.

Heavy Metals in Biota in Delaware Bay, NJ: Developing a Food Web Approach to Contaminants.

Understanding the relationship between heavy metal and selenium levels in biota and their foods is important, but often difficult to determine because animals eat a variety of organisms. Yet such information is critical to managing species populations, ecological integrity, and risk to receptors (including humans) from consumption of certain prey. We examine levels of cadmium, lead, mercury, and selenium in biota from Delaware Bay (New Jersey, USA) to begin construction of a "springtime" food web that focuses on shorebirds. Horseshoe crab (Limulus polyphemus) eggs are one of the key components at the base of the food web, and crab spawning in spring provides a food resource supporting a massive stopover of shorebirds. Fish and other biota also forage on the crab eggs, and a complex food web leads directly to top-level predators such as bluefish (Pomatomus saltatrix) and striped bass (Morone saxatilis), both of which are consumed by egrets, eagles, ospreys (Pandion haliaetus), and humans. Metal levels in tissues were generally similar in algae, invertebrates, and small fish, and these were similar to those in blood of shorebirds (but not feathers). There was a significant direct relationship between the levels of metals in eggs of horseshoe crabs and mean metal levels in the blood of four species of shorebirds. Metal levels in shorebird feathers were higher than those in blood (except for selenium), reflecting sequestration of metals in feathers during their formation. Levels in feathers of laughing gulls (Leucophaeus atricilla) were similar to those in feathers of shorebirds (except for selenium). Selenium bears special mention as levels were significantly higher in the blood of all shorebird species than in other species in the food web, and were similar to levels in their feathers. Levels of metals in bluefish and striped bass were similar or higher than those found in the blood of shorebirds (except for selenium). The mean levels of cadmium, lead, and mercury in the blood and feathers of shorebirds were below any effect levels, but selenium levels in the blood and feathers of shorebirds were higher than the sublethal effect levels for birds. This is a cause for concern, and warrants further examination.

Long-distance migratory shorebirds travel faster towards their breeding grounds, but fly faster post-breeding.

Long-distance migrants are assumed to be more time-limited during the pre-breeding season compared to the post-breeding season. Although breeding-related time constraints may be absent post-breeding, additional factors such as predation risk could lead to time constraints that were previously underestimated. By using an automated radio telemetry system, we compared pre- and post-breeding movements of long-distance migrant shorebirds on a continent-wide scale. From 2014 to 2016, we deployed radio transmitters on 1,937 individuals of 4 shorebird species at 13 sites distributed across North America. Following theoretical predictions, all species migrated faster during the pre-breeding season, compared to the post-breeding season. These differences in migration speed between seasons were attributable primarily to longer stopover durations in the post-breeding season. In contrast, and counter to our expectations, all species had higher airspeeds during the post-breeding season, even after accounting for seasonal differences in wind. Arriving at the breeding grounds in good body condition is beneficial for survival and reproductive success and this energetic constraint might explain why airspeeds are not maximised in the pre-breeding season. We show that the higher airspeeds in the post-breeding season precede a wave of avian predators, which could suggest that migrant shorebirds show predation-minimizing behaviour during the post-breeding season. Our results reaffirm the important role of time constraints during northward migration and suggest that both energy and predation-risk constrain migratory behaviour during the post-breeding season.

Influenza A virus: sampling of the unique shorebird habitat at Delaware Bay, USA.

Delaware (DE) Bay, in the northeastern USA, has long been recognized as a hotspot for avian influenza A virus (IAV); every spring, this coastal region serves as a brief stopover site for thousands of long-distance migrating shorebirds, en route to breeding grounds in the Arctic. During these stopovers, IAV has been consistently recovered from ruddy turnstones (Arenaria interpres) that are likely to become infected as they feed by probing sand and cobble in search of food. In May 2010-2012, we successfully isolated 19 IAV from environmental samples (sand, n = 18; horseshoe crab eggs, n = 1) obtained from DE Bay sites. Two of these viruses were subjected to laboratory conditions similar to those in the DE Bay spring-time environment, and remained infectious for 7 days. Here, through the recovery of IAV from environmental samples, temperature monitoring at and below the sand surface and simulated laboratory trials, we provide evidence that the beach environment may enable localized transmission and short-term maintenance of IAV in this unique ecosystem.

Spring Migration Stopover Ecology of Avian Influenza Virus Shorebird Hosts at Delaware Bay.

Although low pathogenicity avian influenza viruses (LPAIV) are detected in shorebirds at Delaware Bay annually, little is known about affected species habitat preferences or the movement patterns that might influence virus transmission and spread. During the 5-wk spring migration stopover period during 2007-2008, we conducted a radiotelemetry study of often-infected ruddy turnstones (Arenaria interpres morinella; n = 60) and rarely infected sanderlings (Calidris alba; n = 20) to identify locations and habitats important to these species (during daytime and nighttime), determine the extent of overlap with other AIV reservoir species or poultry production areas, reveal possible movements of AIV around the Bay, and assess whether long-distance movement of AIV is likely after shorebird departure. Ruddy turnstones and sanderlings both fed on Bay beaches during the daytime. However, sanderlings used remote sandy points and islands during the nighttime while ruddy turnstones primarily used salt marsh harboring waterfowl and gull breeding colonies, suggesting that this environment supports AIV circulation. Shorebird locations were farther from agricultural land and poultry operations than were random locations, suggesting selection away from poultry. Further, there was no areal overlap between shorebird home ranges and poultry production areas. Only 37% (22/60) of ruddy turnstones crossed into Delaware from capture sites in New Jersey, suggesting partial site fidelity and AIV gene pool separation between the states. Ruddy turnstones departed en masse around June 1 when AIV prevalence was low or declining, suggesting that a limited number of birds could disperse AIV onto the breeding grounds. This study provides needed insight into AIV and migratory host ecology, and results can inform both domestic animal AIV prevention and shorebird conservation efforts.

Mercury, Lead, Cadmium, Arsenic, Chromium and Selenium in Feathers of Shorebirds during Migrating through Delaware Bay, New Jersey: Comparing the 1990s and 2011/2012.

Understanding temporal changes in contaminant levels in coastal environments requires comparing levels of contaminants from the same species from different time periods, particularly if species are declining. Several species of shorebirds migrating through Delaware Bay have declined from the 1980s to the present. To evaluate some contaminants as cause for the declines, we examine levels of mercury, lead, cadmium, arsenic, chromium and selenium in feathers of red knot (Calidris canutus, N = 46 individuals), semipalmated sandpiper (Calidris pusilla, N = 70) and sanderling (Calidris alba, N = 32) migrating through Delaware Bay, New Jersey, USA, from 1991 to 1992 (N = 40), 1995 (N = 28), and 2011-2012 (N = 80) to determine if levels have changed. We found: (1) arsenic, chromium, and lead increased in red knot and decreased in semipalmated sandpiper; (2) cadmium decreased in semipalmated sandpipers; (3) mercury decreased in red knot and sanderlings; (4) selenium decreased in red knot and increased in semipalmated sandpipers. In 2011/2012 there were significant interspecific differences for arsenic, mercury and selenium. Except for selenium, the element levels were well below levels reported for feathers of other species. The levels in feathers in red knots, sanderling, and semipalmated sandpipers from Delaware Bay in 2011/2012 were well below levels in feathers that are associated with effect levels, except for selenium. Selenium levels ranged from 3.0 µg·g-1 dry weight to 5.8 µg·g-1 (semipalmated sandpiper), within the range known to cause adverse effects, suggesting the need for further examination of selenium levels in birds. The levels of all elements were well below those reported for other marine species, except for selenium, which was near levels suggesting possible toxic effects.

Long-term surveillance of H7 influenza viruses in American wild aquatic birds: are the H7N3 influenza viruses in wild birds the precursors of highly pathogenic strains in domestic poultry?

The emergence of influenza A virus (IAV) in domestic avian species and associated transmissions to mammals is unpredictable. In the Americas, the H7 IAVs are of particular concern, and there have been four separate outbreaks of highly pathogenic (HP) H7N3 in domestic poultry in North and South America between 2002 and 2012, with occasional spillover into humans. Here, we use long-term IAV surveillance in North American shorebirds at Delaware Bay, USA, from 1985 to 2012 and in ducks in Alberta, Canada, from 1976 to 2012 to determine which hemagglutinin (HA)-neuraminidase (NA) combinations predominated in Anseriformes (ducks) and Charadriiformes (shorebirds) and whether there is concordance between peaks of H7 prevalence and transmission in wild aquatic birds and the emergence of H7 IAVs in poultry and humans. Whole-genome sequencing supported phylogenetic and genomic constellation analyses to determine whether HP IAVs emerge in the context of specific internal gene segment sequences. Phylogenetic analysis of whole-genome sequences of the H7N3 influenza viruses from wild birds and HP H7N3 outbreaks in the Americas indicate that each HP outbreak was an independent emergence event and that the low pathogenic (LP) avian influenza precursors were most likely from dabbling ducks. The different polybasic cleavage sites in the four HP outbreaks support independent origins. At the 95% nucleotide percent identity-level phylogenetic analysis showed that the wild duck HA, PB1, and M sequences clustered with the poultry and human outbreak sequences. The genomic constellation analysis strongly suggests that gene segments/virus flow from wild birds to domestic poultry.

Avian influenza virus infection dynamics in shorebird hosts.

To gain insight into avian influenza virus (AIV) transmission, exposure, and maintenance patterns in shorebirds at Delaware Bay during spring migration, we examined temporal AIV prevalence trends in four Charadriiformes species with the use of serial cross-sectional data from 2000 through 2008 and generalized linear and additive models. Prevalence of AIV in Ruddy Turnstones (Arenaria interpres morinella) increased after arrival, peaked in mid-late May, and decreased prior to departure. Antibody prevalence also increased over this period; together, these results suggested local infection and recovery prior to departure. Red Knots (Calidris canutus rufa), Sanderlings (Calidris alba), and Laughing Gulls (Leucophaeus atricilla) were rarely infected, but dynamic changes in antibody prevalence differed among species. In Red Knots, declining antibody prevalence over the stopover period suggested AIV exposure prior to arrival at Delaware Bay with limited infection at this site. Antibody prevalence was consistently high in Laughing Gulls and low in Sanderlings. Both viral prevalence and antibody prevalence in Sanderlings varied directly with those in turnstones, suggesting virus spillover to Sanderlings. Results indicate that, although hundreds of thousands of birds concentrate at Delaware Bay during spring, dynamics of AIV infection differ among species, perhaps due to differences in susceptibility, potential for contact with AIV at this site, or prior exposure. Additionally, Ruddy Turnstones possibly act as a local AIV amplifying host rather than a reservoir.

Prevalence of antibodies to type a influenza virus in wild avian species using two serologic assays.

Serologic testing to detect antibodies to avian influenza (AI) virus has been an underused tool for the study of these viruses in wild bird populations, which traditionally has relied on virus isolation and reverse transcriptase-polymerase chain reaction (RT-PCR). In a preliminary study, a recently developed commercial blocking enzyme-linked immunosorbent assay (bELISA) had sensitivity and specificity estimates of 82% and 100%, respectively, for detection of antibodies to AI virus in multiple wild bird species after experimental infection. To further evaluate the efficacy of this commercial bELISA and the agar gel immunodiffusion (AGID) test for AI virus antibody detection in wild birds, we tested 2,249 serum samples collected from 62 wild bird species, representing 10 taxonomic orders. Overall, the bELISA detected 25.4% positive samples, whereas the AGID test detected 14.8%. At the species level, the bELISA detected as many or more positive serum samples than the AGID in all 62 avian species. The majority of positive samples, detected by both assays, were from species that use aquatic habitats, with the highest prevalence from species in the orders Anseriformes and Charadriiformes. Conversely, antibodies to AI virus were rarely detected in the terrestrial species. The serologic data yielded by both assays are consistent with the known epidemiology of AI virus in wild birds and published reports of host range based on virus isolation and RT-PCR. The results of this research are also consistent with the aforementioned study, which evaluated the performance of the bELISA and AGID test on experimental samples. Collectively, the data from these two studies indicate that the bELISA is a more sensitive serologic assay than the AGID test for detecting prior exposure to AI virus in wild birds. Based on these results, the bELISA is a reliable species-independent assay with potentially valuable applications for wild bird AI surveillance.

Angiogenic factors may have a different prognostic role in adult acute lymphoblastic leukemia.

Angiogenesis plays an important role in solid tumors and hematologic malignancies. The prognostic significance of angiogenic factors in adult acute lymphoblastic leukemia (ALL) remains ambiguous. We therefore analyzed the impact of angiogenic factor levels on overall survival of newly diagnosed adult ALL patients. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-1 receptor alpha (IL-1Ralpha), IL-6, IL-8, VEGF receptors VEGFR1 and VEGFR2, and thrombopoietin (TPO) were measured in plasma samples of 95 patients by enzyme-linked immunosorbent assay (ELISA). In a univariate Cox proportional hazards model, higher levels of IL-1Ralpha, IL-8, VEGFR1, and VEGFR2 were predictive of poor survival. In contrast, higher levels of VEGF were predictive of longer survival, and higher levels of bFGF suggested a similar trend (P = .09). The multivariate model simultaneously included VEGF (relative risk [RR] for death, 8.01; P = .001 for levels less than or equal to 19.5 pg/mL), IL-1Ralpha (RR, 5.12; P = .007 for levels greater than 373 pg/mL), and VEGFR2 (RR, 4.01; P = .04 for levels greater than 8222 pg/mL) as independent factors for survival. Of interest is the association of high levels of VEGF with good prognosis and higher levels of VEGF receptors with poor outcome. These data reflect the complexity by which angiogenic factors may affect the clinical behavior of patients with ALL, and this complexity should be considered in any therapeutic strategy incorporating antiangiogenic agents.

Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myelodysplastic syndromes.

BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) are major regulators of angiogenesis, which plays a key role in the growth and dissemination of solid tumors and hematologic neoplasms. METHODS: The authors measured the plasma concentrations of soluble VEGFR1 (sVEGFR1) and sVEGFR2 in 133 patients with acute myeloid leukemia (AML) and in 80 patients with myelodysplastic syndromes (MDS) at the time of initial presentation and compared clinical behaviors. RESULTS: A reverse correlation was observed between plasma sVEGFR1 levels and the rate of complete remission (CR) in patients with AML, but not in patients with MDS. In contrast, increased plasma levels of sVEGFR2 were correlated with a lower CR rate in patients with MDS, but not in patients with AML. Cox regression model analysis demonstrated that plasma levels of sVEGFR1, but not sVEGFR2, were independent prognostic factors in both patients with AML and patients with MDS. CONCLUSIONS: The findings suggest that different mechanisms are involved in the pathophysiology of AML and MDS. The concentration of sVEGFR1 and sVEGFR2 in plasma should be considered a significant factor in guiding antiangiogenic therapy for AML and MDS. They may play a role in the pharmacodynamics of therapeutic agents that are supposed to bind directly to these receptors.

Relative increase in leukemia-specific DNA in peripheral blood plasma from patients with acute myeloid leukemia and myelodysplasia.

Using loss of heterozygosity (LOH) and X-chromosome inactivation, we compared peripheral blood (PB) plasma with bone marrow (BM) cells in detecting genomic abnormalities in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We detected LOH in the PB plasma of all 45 patients who had cytogenetically documented chromosomal abnormalities (5q-, 7-, +8, 17-, or 20-). BM cells from the same patients showed LOH in 89% of patients with MDS and 70% of patients with AML. Posttherapy samples from 16 of these patients demonstrated complete concordance between LOH and cytogenetics in detecting residual disease in 15 samples. Of the 16 samples, 4 showed LOH in plasma with normal BM morphology. Using X-chromosome inactivation, clonality was detectable in 19 (73%) of 26 BM samples, whereas all PB plasma samples showed clonality. These data support the conclusion that PB plasma is enriched by tumor-specific DNA and can replace BM cells for studying genomic abnormalities.

Increased apoptosis in bone marrow B lymphocytes but not T lymphocytes in myelodysplastic syndrome.

The hallmark of myelodysplastic syndrome (MDS) is enhanced apoptosis in myeloid, erythroid, and megakaryocytic cells in the bone marrow leading to ineffective hematopoiesis. Recent studies suggested that immunological and microenvironmental factors play a role in the pathophysiology of this disease. We report a significant increase in apoptosis in bone marrow B lymphocytes in MDS as compared to that found in acute myeloid leukemia and healthy controls. Furthermore, we demonstrate that patients with refractory anemia with excess blasts in transformation (RAEB-T) had apoptosis levels in lymphocytes similar to those seen in other subtypes of MDS. Our findings suggest that the alterations in B lymphocytes in the form of increased apoptosis can be seen in MDS and support the concept that immune modulation plays a role in the pathophysiology of MDS.