Blood cancer, kill yourself!
To cope with leukemia, you need to strengthen it
Immature lymphocytes, the precursors of B and T cells, become a source of trouble. However, most cases of lymphoblastic leukemia occur precisely in B-variants, when it is the immature B-cells that lose control over themselves and begin to divide uncontrollably. In many cases, chemotherapy helps, but it happens (especially in cases of "adult" leukemia) that the disease is associated with a genetic defect, because of which conventional treatments are powerless.
This defect is called the Philadelphia chromosome: two chromosomes, 9 and 22, exchange sites, and as a result, the activity of a certain enzyme in the cell increases, which triggers malignant degeneration. How does it work? We know that it is the duty of B cells to synthesize antibodies against infection, which they should feel in time. They have special receptors on the cell membrane that respond to "alarm signals" from the outside and trigger cell division – after all, once we have an infection, the number of immune cells needs to be increased. The work of the receptors themselves is controlled by a special verification system. If they function poorly, then such a cell is rejected, it is simply useless. But even if the receptors work too hard, the cell is also rejected – if it is left, its descendants, for good, will launch autoimmune aggression against our own tissues and organs.
The action of an oncogenic enzyme mimics a receptor reaction: the precursors of B cells begin to multiply actively, as if in response to an infection (which in fact does not exist), but at the same time they do not reach the state of a mature cell. At first glance, the treatment strategy here suggests itself: you need a remedy that would suppress the activity of a harmful enzyme. Such a tool called imatinib was really created. However, the usual problem of oncological diseases followed: the malignant cells began to develop resistance to the drug.
Of course, you can try to create a new therapeutic substance of the same principle of action, only stronger. However, researchers from the University of California at San Francisco have proposed a completely different method to combat lymphoblastic leukemia - they tried to get rid of the disease using the aforementioned quality control system, which rejects immature B cells that are too active. That is, the signal that causes the cell to divide must actually be made even stronger in order to include in it a self-destruction program that prevents autoimmune disorders (UCSF News, To Beat Leukemia, Boost Cell Signaling, Study Suggests).
Markus Muschen and his colleagues tested such a signal booster on mice with a stable form of leukemia. In an article in Nature (Chen et al., Signaling thresholds and negative B-cell selection in acute lymphoblastic leukaemia), the authors write that malignant cells really disappeared, the symptoms of the disease weakened significantly and the animals stayed alive much longer than without treatment. The remedy had time to act only on sick lymphocytes, ordinary, healthy cells remained intact. This selectivity distinguishes the new drug favorably from conventional chemotherapeutic drugs, from which both diseased tissues and healthy ones suffer. However, before clinical trials begin, it will be necessary to make sure that such strong stimulation of the receptors does not harm the immune system. The principle of action itself has justified itself, but it is possible that people will need to come up with their own analogue of this substance. And, of course, I would like to hope that in this way it will be possible to treat not only cases of drug-resistant leukemias that have developed due to the appearance of the Philadelphia chromosome, but also other types of B-cell oncological diseases of the blood.
Portal "Eternal youth" http://vechnayamolodost.ru30.03.2015