Interesting Article from the latest LLS new letter

[Guest guest]

Hi Everyone,

Although this testing method can now only be used in research, my hope

is that it will be fast-tracked soon.

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Hutchinson Cancer Research Center Researcher Develops Method for Early

Detection of Leukemia Relapse

Thursday July 10, 11:31 am ET

Fluidigm Digital Arrays Allow 1000X Improvement in Detection

Sensitivity of PCR Reactions

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Researchers at the Fred

Hutchinson Cancer Research Center have developed a method that allows

for the early detection of a common mechanism of resistance on drug

treatment for chronic myeloid leukemia. The authors were able to

detect a specific point mutation, which is associated with acquired

resistance to the drugs Gleevec (imatinib mesylate), Sprycel

(dasatinib), and Tasigna (nilotinib), as much as 100 days earlier than

standard tests used in clinical practice today. In the future, this

strategy could allow doctors to identify early relapse with this

mutation (as well as others) and consider changing to alternatives

earlier in treatment than they can now.

Today's issue of Nature Magazine's journal, Leukemia, discloses the

work of Vivian Oehler, M.D. and Jerald Radich, M.D. of the Fred

Hutchinson Cancer Research Center. In the letter, Dr. Oehler describes

how she uses a Fluidigm integrated fluidic circuit (called a digital

array). " Using this method, we can detect just a few mutated molecules

in the background of as many as 100,000 molecules. It is a little like

looking for a needle-in-a-haystack by first dividing the haystack into

many smaller haystacks, which makes it easier to find the needle, "

explained Dr. Oehler. The Fluidigm Digital Array uses nanoscale

channels, valves and pumps to partition samples into up to 9,180

chambers prior to PCR.

As a consequence of this partitioning, a mixture containing one

molecule of T3151 ABL in 100,000 molecules of unmutated ABL is

separated into 1000 independent chambers. " The chamber containing the

single mutant molecule now only contains approximately 100 molecules

of unmutated ABL, " explained Ramesh Ramakrishnan, Ph.D., Fluidigm's

Director of Molecular Biology. " This 1000-fold increase in relative

concentration theoretically allows for a 1000-fold improvement in the

detection sensitivity of PCR reactions. "

The most common method used in clinical practice today is direct

nucleotide sequencing. This method requires at least a 20 percent

concentration of mutated molecules to be present in order to detect

them. The problem with this method is that by the time mutations are

usually detected, a relapse has already occurred. " With this new

method we hope to move up the window of detection. In our studies we

specifically looked at the T315I mutation first as currently all

tyrosine kinase inhibitors are resistant to it, but we have designed

assays for other mutations associated with poor prognosis as well, "

said Dr. Oehler.

About Fluidigm

Fluidigm develops, manufactures and markets proprietary Integrated

Fluidic Circuit (IFC) systems that significantly improve productivity

in life science research. Fluidigm's IFCs enable the simultaneous

performance of thousands of sophisticated biochemical measurements in

extremely minute volumes. These " integrated circuits for biology " are

made possible by miniaturizing and integrating liquid handling

components on a single microfabricated device. Fluidigm's IFC systems,

consisting of instrumentation, software and single-use IFCs, increase

throughput, decrease costs and enhance sensitivity compared to

conventional laboratory systems. Fluidigm products have not been

cleared or approved by the Food and Drug Administration for use as a

diagnostic and are only available for research use.

Blessings,

Don