Sensitive and Specific Measurement of Minimal Residual Disease in Acute Lymphoblastic Leukemia

A sensitive and specific quantitative real-time polymerase chain reaction method, involving three rounds of amplification with two allele-specific oligonucleotide primers directed against an rearrangement, was developed to quantify minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (ALL). For a single sample containing 10 μg of good quality DNA, MRD was quantifiable down to approximately 10−6, which is at least 1 log more sensitive than current methods. Nonspecific amplification was rarely observed. The standard deviation of laboratory estimations was 0.32 log units at moderate or high levels of MRD, but increased markedly as the level of MRD and the number of intact marker gene rearrangements in the sample fell. In 23 children with ALL studied after induction therapy, the mean MRD level was 1.6 × 10−5 and levels ranged from 1.5 × 10−2 to less than 10−7. Comparisons with the conventional one-round quantitative polymerase chain reaction method on 29 samples from another 24 children who received treatment resulted in concordant results for 22 samples and discordant results for seven samples. The sensitivity and specificity of the method are due to the use of nested polymerase chain reaction, one segment-specific and two allele-specific oligonucleotide primers, and the use of a large amount of good quality DNA. This method may improve MRD-based decisions on treatment for ALL patients, and the principles should be applicable to DNA-based MRD measurements in other disorders

Multi-Source EO for Dynamic Wetland Mapping and Monitoring in the Great Lakes Basin

Wetland managers, citizens and government leaders are observing rapid changes in coastal wetlands and associated habitats around the Great Lakes Basin due to human activity and climate variability. SAR and optical satellite sensors offer cost effective management tools that can be used to monitor wetlands over time, covering large areas like the Great Lakes and providing information to those making management and policy decisions. In this paper we describe ongoing efforts to monitor dynamic changes in wetland vegetation, surface water extent, and water level change. Included are assessments of simulated Radarsat Constellation Mission data to determine feasibility of continued monitoring into the future. Results show that integration of data from multiple sensors is most effective for monitoring coastal wetlands in the Great Lakes region. While products developed using methods described in this article provide valuable management tools, more effort is needed to reach the goal of establishing a dynamic, near-real-time, remote sensing-based monitoring program for the basin

Multi-Source EO for Dynamic Wetland Mapping and Monitoring in the Great Lakes Basin

Wetland managers, citizens and government leaders are observing rapid changes in coastal wetlands and associated habitats around the Great Lakes Basin due to human activity and climate variability. SAR and optical satellite sensors offer cost effective management tools that can be used to monitor wetlands over time, covering large areas like the Great Lakes and providing information to those making management and policy decisions. In this paper we describe ongoing efforts to monitor dynamic changes in wetland vegetation, surface water extent, and water level change. Included are assessments of simulated Radarsat Constellation Mission data to determine feasibility of continued monitoring into the future. Results show that integration of data from multiple sensors is most effective for monitoring coastal wetlands in the Great Lakes region. While products developed using methods described in this article provide valuable management tools, more effort is needed to reach the goal of establishing a dynamic, near-real-time, remote sensing-based monitoring program for the basin

Determining the Repertoire of IGH Gene Rearrangements to Develop Molecular Markers for Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia

Molecular markers for minimal residual disease in B-lineage acute lymphoblastic leukemia were identified by determining, at the time of diagnosis, the repertoire of rearrangements of the immunoglobulin heavy chain (IGH) gene using segment-specific variable (V), diversity (D), and junctional (J) primers in two different studies that involved a total study population of 75 children and 18 adults. This strategy, termed repertoire analysis, was compared with the conventional strategy of identifying markers using family-specific V, D, and J primers for a variety of antigen receptor genes. Repertoire analysis detected significantly more markers for the major leukemic clone than did the conventional strategy, and one or more IgH rearrangements that were suitable for monitoring the major clone were detected in 96% of children and 94% of adults. Repertoire analysis also detected significantly more IGH markers for minor clones. Some minor clones were quite large and a proportion of them would not be able to be detected by a minimal residual disease test directed to the marker for the major clone. IGH repertoire analysis at diagnosis has potential advantages for the identification of molecular markers for the quantification of minimal residual disease in acute lymphoblastic leukemia cases. An IGH marker enables very sensitive quantification of the major leukemic clone, and the detection of minor clones may enable early identification of additional patients who are prone to relapse