New Method of testing for earlier signs of relapse

[Guest guest]

Hey folks

I just got the new issue if LLS Newletter. Maybe some of you get it too,

but there is an excitig article on earlier detection of relapse. I am

enclosing it here.

Barb

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.

For more information, please visit www.Fluidigm.com

<http://www.fluidigm.com/> .