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Late-Breaking Data Highlighting Research Advances in Several Blood Disorders to Be Presented At the American Society of Hematology Annual Meeting
Date:12/6/2008

bset of patients (85 percent) had an overproduction of malignant cells mainly dependent on the late stages of blood cell differentiation, far downstream from the stem cell. In contrast, a second subset of patients (15 percent) had an early expansion of very immature malignant progenitor cells, close to the stem cell.

Researchers then hypothesized that the second subset of patients had a pre-existent molecular defect able to promote the early expansion of the malignant cells. With high-resolution arrays, researchers were able to identify one single gene, TET2, which belongs to a family of three genes of unknown function.

Researchers then further analyzed cells in five patients with TET2mutations, which demonstrated that TET2 defects target hematopoietic stem cells. Moreover, they show that in these five patients TET2 inactivation precedes the JAK2 V617Fmutation, suggesting that this new molecular lesion could be an early event in cancer stem cell formation.

To further test these findings, researchers sequenced TET2in 181 unselected JAK2 V617F patients with myeloproliferative disorders. TET2 mutations were found in 25 of the 181 patients, resulting in an overall 14 percent frequency.

Tetrahydrobiopterin (6R-BH4): Novel Therapy forEndothelial Dysfunction in Sickle Cell Disease

[LBA-5]

Lewis Hsu, M.D., Ph.D., Drexel University, Philadelphia, PA

*Abstract LBA-5 is being presented on Saturday, December 6, at 9:30 a.m. at the ASH press conference on advances in screening and treatment for sickle cell disease. The embargo for this abstract will break at that time.

The results of this phase II study showed that the investigational oral agent tetrahydrobiopterin is safe and well-tolerated. The drug
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SOURCE American Society of Hematology
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