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Minimal residual disease detected in nearly double the number ofleukemia patients using high-throug by airbru airbru





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Minimal residual disease detected in nearly double the number ofleukemia patients using high-throug by
Article Posted: 11/14/2013
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Minimal residual disease detected in nearly double the number ofleukemia patients using high-throug


 
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A study led by researchers at Fred Hutchinson Cancer ResearchCenter has found that a next-generation, high-speed DNA-decodingtechnology called high-throughput sequencing can detect theearliest signs of potential relapse in nearly twice the number of leukemia patients as compared to flow cytometry, the current gold standardfor detecting minimal residual disease. The results of the study,led by Hutchinson Center computational biologist Harlan Robins,Ph.D., are reported in Science Translational Medicine. "The ability to predict disease relapse sooner with high-throughputsequencing would give hematologists the option to treat cancer recurrence earlier, offering a greater chance of survival. Longerterm, this technology potentially also could be used to initiallydiagnose leukemia and lymphoma much earlier than we can today," said Robins, an associate memberof the Hutchinson Center's Public Health Sciences Division andcorresponding author of the paper. For the study, Robins and colleagues compared the effectiveness ofhigh-throughput sequencing versus flow cytometry to detect minimalresidual disease in 43 patients diagnosed with acute Tlymphoblastic leukemia, a type of blood cancer that is most commonin children under age 7.

By sequencing the patients' T-cellreceptor genes before and 29 days after chemotherapy, theresearchers were able to precisely measure their presence in theblood and provide a more accurate prediction of leukemia relapse. "The high-throughput sequencing detected minimal residual diseasein nearly double the number of patients than flow cytometry - 22versus 12 patients, respectively," Robins said. Minimal residual disease, or MRD, a major predictor of cancerrelapse, is when a small number of cancer cells survive treatmentand persist in patients. Until recently, MRD was undetectable.

Flowcytometry, the primary method for detecting MRD in the UnitedStates, counts the number of cells in the blood withcancer-specific protein markers on their surface. While it isconsidered the gold standard, flow cytometry comes with a number oflimitations: it has been difficult to standardize across different labs becausethere is no standard protocol; the antibodies used to tag the cancerous cells are expensive; every cancer type requires a different test, because eachmalignancy is associated with a different protein marker; and the sensitivity of the test is low, which means it sometimes failsto recognize the presence of cancer cells. This study - the first use of high-throughput sequencing, or HTS,to detect minimal-residual disease in a clinical trial setting -found it to be at least 20 times more sensitive than flow cytometryin detecting MRD. "Our research indicates that HTS offers many advantages over flowcytometry," Robins said. "Since HTS can detect any pre-identifiedclone and is performed in a centralized lab, it consistentlygenerates reproducible and reliable results regardless of cancertype, using the same process for disease detection and tracking.Furthermore, HTS is highly automated, cost-effective and objective,whereas flow cytometry is more time consuming, relies on the skillof the operator and is therefore subject to human error." The Hutchinson Center has patents pending on core technologiesemployed by Robins and colleagues in conjunction withhigh-throughput DNA-sequencing used for this study.

These coretechnologies have been licensed exclusively to AdaptiveBiotechnologies, a Seattle biotechnology company Robins co-foundedthat offers commercial DNA sequencing and analysis. Robins and colleagues discovered how to adapt traditionalhigh-throughput technology to sequence only variable regions of thehuman genetic code: the T- and B-cell receptors - a criticalcomponent of the human adaptive immune system. These receptors areshort strands of DNA that constantly rearrange to allow the immunesystem to fight viruses, infection or disease. "This discovery was critical to our understanding of how patientsmount immunological responses against cancer, autoimmune disordersand infectious diseases," said Robins, whose Hutchinson Centerresearch focuses on the genetics of the immune system -particularly how it responds to pathogens and the aging process. Additional References Citations.

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