Published in the May edition of the Journal of Virology, the discovery may lead to new drugs to prevent sexually transmitted HIV infection.

"Dendritic cells act like sentries to alert the immune system when a foreign agent tries to infiltrate the body," said Dr. Benhur Lee, UCLA assistant professor of microbiology, immunology and molecular genetics. "They also produce a molecule called DC-SIGN that plays a critical role in the sexual transmission of HIV. We wanted to see what would happen if we blocked how DC-SIGN functions in its natural environment."

Dendritic cells reside in the mucosal linings of the mouth, gut, genital and urinary tracts -- sites where sexually transmitted HIV often enters the body. By examining biopsies of human rectal tissues, the UCLA team was the first to study DC-SIGN on dendritic cells in their natural setting instead of a test tube.

Using a sugar-like compound that binds to DC-SIGN and a DC-SIGN-seeking antibody, the scientists were able to block HIV from binding to these dendritic cells.

"Our findings suggest that preventing HIV from binding to the dendritic cells may block their ability to carry HIV to other parts of the immune system," Lee said. "Our next step will be to investigate if this is true."

"We believe our findings point to a new therapeutic target for preventing HIV infection," said Dr. Peter Anton, UCLA professor of medicine. "Drugs could be developed to block the interaction between HIV and DC-SIGN, potentially reducing HIV's ability to spread infection at mucosal routes into the body."

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Some leukemia patients carry rearrangements of a gene on chromosome 11 called the mixed lineage leukemia gene, or MLL. Translocations involving MLL are most often found in childhood leukemias and as a secondary cancer in adults who have undergone chemotherapy to treat a previous leukemia.

Individuals with MLL translocations have an especially poor prognosis, with less than a 50 percent survival rate.

"There are more than 40 proteins that have been found fused to MLL in leukemia patients, and different ones can cause leukemia by different mechanisms," Zhang said.

When MLL functions as it should, without a fusion partner, it binds to and controls the expression of Hox genes, which in turn control cell growth and maturation. Until now, the role of the MLL-AF10 fusion protein in causing leukemia was unknown.

"We show how at least one MLL fusion can lead to the over-expression of Hox genes in bone marrow cells. MLL-AF10 directs hDOT1L to the Hox genes, where it normally shouldn't be, causing a different pattern of histone methylation and, therefore, extraordinarily high activity of the Hox genes," Zhang said.

Treatments used for AML patients have been largely ineffective against cells harboring the MLL-AF10 fusion protein, drawing attention to the need for a new medication.

Zhang's study reveals that leukemia cells containing MLL-AF10 require hDOT1L to survive. When the researchers introduced into leukemia cells a defective form of hDOT1L, one that cannot methylate histone proteins, the cells were no longer able to grow. "This study highlights the potential of hDOT1L as a possible drug target," Zhang added.

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