Researchers engineer a ‘cancer differentiation therapy’ for leukemia.


Researchers at the Stanford University have discovered that when a certain aggressive leukemia is causing havoc in the body, the solution may be to force the cancer cells to grow up and behave.  After a chance observation in the lab, the researchers found a method that can cause dangerous leukemia cells to mature into harmless immune cells known as macrophages.  The study is published in the Proceedings of the National Academy of Sciences.

B-cell acute lymphoblastic leukemia with a mutation called the Philadelphia chromosome is a particularly aggressive cancer with poor outcomes state the team, so finding potential treatments is particularly exciting.

The researchers made the key observation after collecting leukemia cells from a patient and trying to keep the cells alive in a culture plate.  They were throwing everything at them to help them survive when they noted that some of the cancer cells in culture were changing shape and size into what looked like macrophages.  The team looked at previous studies, which showed that early B-cell mouse progenitor cells could be forced to become macrophages when exposed to certain transcription factors, proteins that bind to certain DNA sequences.

The team explain that B-cell leukemia cells are in many ways progenitor cells that are forced to stay in an immature state. So they did more experiments and confirmed that methods shown to have altered the fate of the mouse progenitor cells years ago could be used to transform these human cancer cells into macrophages, which can engulf and digest cancer cells and pathogens.

It is hoped that when the cancer cells become macrophages they will not only be neutralized, but may actually assist in fighting the cancer. Like a bloodhound owner who gives the dog a sniff of an object that was associated with the person or animal to track, macrophage cells present recognizable bits of abnormal cells to other immune cells so that they can launch an attack.  Because the macrophage cells came from the cancer cells, they will already carry with them the chemical signals that will identify the cancer cells, making an immune attack against the cancer more likely, the team theorise.

The researchers’ next steps will be to see if they can find a drug that will prompt the same reaction and that could serve as the basis for a therapy for the leukemia. There is some precedent for such a treatment. Retinoic acid is commonly used to treat another cancer called acute promyelocytic leukemia. In that case, retinoic acid is used to turn cancer cells into mature cells called granulocytes. This treatment is the only well-established therapy that matures, or ‘differentiates,’ cancer cells, but researchers around the world are hopeful of finding many more.  There’s big-time interest in differentiation therapies for cancer.

Source:  Stanford University School of Medicine

FACS-purified CD14+CD11b+ cells from human samples demonstrate morphologic and biochemical hallmarks of myeloid cells.  Freshly thawed (day&0) patient samples were sorted for CD19+CD34+ blasts and CD14+CD11b+ myeloid cells.  A. The FACS-purified cells of three patient samples were examined with Wright-Giemsa staining (top panels; bar, 20um) or nitroblue tetrazolium (NBT, bottom panels).  Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages.  Majeti et al 2015.

FACS-purified CD14+CD11b+ cells from human samples demonstrate morphologic and biochemical hallmarks of myeloid cells. Freshly thawed (day&0) patient samples were sorted for CD19+CD34+ blasts and CD14+CD11b+ myeloid cells. A. The FACS-purified cells of three patient samples were examined with Wright-Giemsa staining (top panels; bar, 20um) or nitroblue tetrazolium (NBT, bottom panels). Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages. Majeti et al 2015.

3 comments

  • Dear Mitchell Petersen,
    This is a wonderful research of blood cancer, leukemia. Many cancer cells dye after radiation therapy but if you grow cancer cells into macrophages then these macrophages will certainly destroy or eat cancer cells. However, it will take some time to see the necessary results. Research works at Harvard in Boston and Stanford University in San Francisco, California, are the best at present.We are sure one day we will control the growth of cancer cells in animals as well as in humans. The new magnetic field therapy is also very encouraging at present to remove cancer cells blood from red hemoglobin iron containing healthy blood cells. The magnetic field attracts healthy red cells with Fe-containing hemoglobin and are attached at the walls of nano tubes as nano particles. When the magnetic field is off then nano tubes can be washed with water and dilute saline and are transfused back in the body of a cancer subject. The cancer cells do not contain iron (Fe) heme particle in hemoglobin and are drained first from the nano tube in a bottle and kept aside. Only good blood with hemoglobin is used for the transfusion process in the body of cancer subject.
    This is a nano technology in which you can separate bad (cancer) blood from good (healthy) blood inside or outside of the body sterilized blood bottles. This is a nano medicine technique of cancer care and magnetic field therapy. Try to learn more on the magnetic therapy and cancer care. This will be future of cancer research on earth and in space for astronauts of America and other nations. You can use this method for leukemia care untill you get macrophages formed in the blood of leukemic person. Manohar DrThakur

    Like

  • Dr.M.Jagesh Kamath

    http://www.iisc.ernet.in/currsci/aug252004/491.pdf

    Some years ago Dr.B.V.Shenoi of Kolar Gold Fields, India had done innovative research in this field. Your work seems to corroborate to this earlier work.

    Like

  • http://www.iisc.ernet.in/currsci/aug252004/491.pdf

    This work of Dr.B.V.Shenoi seems to corroborate with this work.

    Like

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