Predicting cancer relapse: Study finds high-throughput sequencing bests flow cytometry

May 16, 2012, Fred Hutchinson Cancer Research Center

A study led by researchers at Fred Hutchinson Cancer Research Center has found that a next-generation, high-speed DNA-decoding technology called high-throughput sequencing can detect the earliest signs of potential relapse in nearly twice the number of leukemia patients as compared to flow cytometry, the current gold standard for detecting minimal residual disease. The results of the study, led by Hutchinson Center computational biologist Harlan Robins, Ph.D., are reported in the May 16 issue of Science Translational Medicine.

"The ability to predict disease relapse sooner with high-throughput sequencing would give hematologists the option to treat earlier, offering a greater chance of survival. Longer term, this technology potentially also could be used to initially diagnose leukemia and lymphoma much earlier than we can today," said Robins, an associate member of the Hutchinson Center's Public Health Sciences Division and corresponding author of the paper.

For the study, Robins and colleagues compared the effectiveness of high-throughput sequencing versus flow cytometry to detect minimal in 43 patients diagnosed with acute T lymphoblastic leukemia, a type of that is most common in children under age 7. By sequencing the patients' genes before and 29 days after chemotherapy, the researchers were able to precisely measure their presence in the blood and provide a more accurate prediction of leukemia relapse.

"The high-throughput sequencing detected minimal residual disease in nearly double the number of patients than flow cytometry – 22 versus 12 patients, respectively," Robins said.

Minimal residual disease, or MRD, a major predictor of cancer relapse, is when a small number of cancer cells survive treatment and persist in patients. Until recently, MRD was undetectable.

Flow cytometry, the primary method for detecting MRD in the United States, counts the number of cells in the blood with cancer-specific protein markers on their surface. While it is considered the gold standard, flow cytometry comes with a number of limitations:

  • it has been difficult to standardize across different labs because there is no standard protocol;
  • the antibodies used to tag the cancerous cells are expensive;
  • every cancer type requires a different test, because each malignancy is associated with a different protein marker; and
  • the sensitivity of the test is low, which means it sometimes fails to 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 cytometry in detecting MRD.

"Our research indicates that HTS offers many advantages over flow cytometry," Robins said. "Since HTS can detect any pre-identified clone and is performed in a centralized lab, it consistently generates reproducible and reliable results regardless of cancer type, 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 skill of the operator and is therefore subject to human error."

The Hutchinson Center has patents pending on core technologies employed by Robins and colleagues in conjunction with high-throughput DNA-sequencing used for this study. These core technologies have been licensed exclusively to Adaptive Biotechnologies, a Seattle biotechnology company Robins co-founded that offers commercial DNA sequencing and analysis.

Robins and colleagues discovered how to adapt traditional high-throughput technology to sequence only variable regions of the human genetic code: the T- and B-cell receptors – a critical component of the human adaptive immune system. These receptors are short strands of DNA that constantly rearrange to allow the immune system to fight viruses, infection or disease.

"This discovery was critical to our understanding of how patients mount immunological responses against , autoimmune disorders and infectious diseases," said Robins, whose Hutchinson Center research focuses on the genetics of the immune system – particularly how it responds to pathogens and the aging process.

Explore further: Chemotherapy may influence leukemia relapse: research

Related Stories

Chemotherapy may influence leukemia relapse: research

January 11, 2012
The chemotherapy drugs required to push a common form of adult leukemia into remission may contribute to DNA damage that can lead to a relapse of the disease in some patients, findings of a new study suggest.

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.