In Real Science

Nicholas J Albertini

The Japanese funded FANTOM international consortium has published a report of its research into genetic regulation of human cellular differentiation this week in Nature Genetics. The group studied the differentiation of human Leukemia cells into white blood cells in groundbreaking detail. They tracked the levels of specific mRNA molecules – precursors to functional proteins – during differentiation.
These mRNA molecules were linked to transcription factors, genetic regulatory proteins responsible for activation and deactivation of genes during cell differentiation. The study reports a timeline of mRNA activity that appears to demonstrate the entire process of gene transcription throughout this type of differentiation. The group also analyzed portions of the cells’ genomic sequence which the transcription factors were likely to activate and compared them to genes lying near these sites in the sequence.
Genes that were close in the sequence to these activation sites transcribed other detected mRNA molecules. A separate experimental verification was done to insure that specific transcription factors identified by the mRNA timeline in cross-analysis with the genome did in fact activate those genes.
Japan has spent about $50 million on this project so far. The processes developed by the FANTOM group are more important than this published report. Their methods for studying gene regulation in cellular differentiation can now be applied to stem cell research. So much work has been done to generate perfectly differentiable stem cells, while the process of their differentiation is still ill-understood.
Though stem cells will usually differentiate into adult cells similar to those in proximity to them, methods of otherwise inducing specific desired differentiation are not known. The methods developed by the FANTOM group could allow for a much better understanding of this process and lead to better stem cell therapies.
A team led by Richard Junghans of the Roger Williams Medical Center has demonstrated a radical new cancer treatment in human subjects. The team treated two patients with prostate cancer who had had their prostates removed surgically. These patients still had measurable amounts of prostate-specific antigen in their blood after the surgery, indicating that prostate cancer cells remained in their bodies.
The researchers used a virus to genetically reprogram some of the patients’ cytotoxic T cells, a type of white blood cell, to destroy cells displaying a marker protein found on the surfaces of prostate cells. This surface protein remained on the cancer cells.
When the engineered T cells were injected into the patients the levels of PSA in their blood dropped significantly. The number of cells injected in this early study was very low, as the study was meant to verify the safety of the procedure. The T cells were likely to live only a few days after injection and the procedure was only preformed once on each subject. Future studies will likely use a higher dose and prolonged treatment.
This procedure sounds very good and it seems to be effective. Other studies will be necessary to insure the safety and effectiveness of this treatment, but intuitively it should be very safe and effective. Cytotoxic T cells are a major part of the body’s immune defense against cancer. Most cells that develop into cancer in the body are killed by T cells before they can cause problems or proliferate.
Cancer cells can only proliferate if they are ignored by T cells. Genetically altering a patient’s own T cells to recognize cancer cells that were previously ignored and reestablishing them in the patient should almost undoubtedly cure the cancer.
If it is easy to engineer the T cells to kill a multitude of cancers without harming any other cells, then this is a viable cure for cancer.

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