Agent Selectively Targets Malignant B Cells In Chronic Leukemia, Study Shows

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Posted 5/3/2011

COLUMBUS, Ohio – A new experimental drug selectively kills the

cancerous cells that cause chronic lymphocytic leukemia, according to a new

study by researchers at the Ohio State University Comprehensive Cancer Center –

Arthur G. Cancer Hospital and J. Solove Research Institute (OSUCCC

– ).

The study shows that the experimental agent PCI-32765 selectively

kills the malignant B lymphocytes that cause chronic lymphocytic leukemia (CLL).

The researchers say the findings, published online in the journal

Blood, are important because current CLL therapies kill T lymphocytes along with

the cancerous B lymphocytes.

T lymphocytes and B lymphocytes make up the adaptive immune system.

When CLL treatment destroys them both, patients become highly susceptible to

life-threatening infections.

“A drug that kills malignant B lymphocytes and spares T lymphocytes

could dramatically improve outcomes for CLL patients,” says study leader Dr.

C. Byrd, director, division of hematology and professor of medicine, of

medicinal chemistry and of veterinary biosciences at the OSUCCC – .

“Our collective results indicate that PCI-32765 is an outstanding

candidate for further development as a therapeutic for CLL,” says study

co-director Dr. Amy J. , assistant professor of hematology and medicinal

chemistry, and a CLL researcher with the OSUCCC-.

The research by Byrd, and a group of colleagues used CLL

cells from ten patients. It had several key findings related to PCI-32765:

a.. The agent specifically targets an important signaling molecule

called Bruton’s tyrosine kinase, which is overexpressed in CLL cells and absent

in T cells.

b.. The agent inhibits the proliferation of CLL cells in

laboratory culture and promotes their death by self-destruction (apoptosis).

c.. It blocks survival signals from cells in the surrounding

microenvironment, including soluble factors such as IL-6, IL-4, and TNF-a, and

stromal-cell contact.

Full story

http://medicalcenter.osu.edu/mediaroom/Pages/release.aspx?newsID=6555