Morphing B-cell leukemia cells into healthy machrophages

Although the article uses B-cell acute lymphoblastic leukemia as an example for morphing the cancer cells into healthy, functional macrophages, the fact that CLL/SLL is also comprised of immature B cells, might work for us too. In CLL/SLL, I am afraid there would be many more problems to overcome given the variety of clones to mention only one but in principle this is an intriguing approach that uses the cancer's own cell progeny to attack itself. Seppuku or turncoats, either way works for me. That's the kind of poetic justice in a therapy development I could really enjoy.

biosciencetechnology.com/ne...

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  • That's really pretty surprising! But then, both macrophages and B-cells start off as hematopoietic stem cells, and their career choice is made for them by what they experience in the marrow.

    Majeti makes a bold statement:

    “B-cell leukemia cells are in many ways progenitor cells that are forced to stay in an immature state,”

    I think that's true of Acute Lymphoblastic Leukemia cels, but its not always true of CLL. CLL cells can be fairly mature - mutated heavy chains are a sign of maturity. So maturity is a relative thing. The blast stage is an earlier stage.

    Macrophages are not necessarily nice guys, either - they can stimulate inflammation and encourage tumor growth:

    en.wikipedia.org/wiki/Macro...

    So I'll wait to see how this research progresses.

  • If "taming" our cancerous B lymphocytes is ever tried it might only work with the unmutated patients which would pertain to your view of relatively naive cells that have yet to pass through the germinal centers.

    I am wondering if the smart money for CLL cure or longterm management would be on a transcriptome based therapy, individualized to address ribosome assembly? Whatever gives heterogeneity to CLL gives the cancer its strength to manifest so uniquely and that instability to my uncredentialed view, points to assembly defects early in the maturation process. The number of chromosomal aberrations being more of a symptom of the underlying assembly defects. I just don't believe one can ignore all the autoimmune issues that co-exist with CLL and not have them all with a common genesis.

    I would agree with your skepticism when comparing a blast phase of leukemia to that of CLL but I am a romantic at heart and could not resist the beauty of the approach.

    WWW

  • I had the same thought as Seymour; the different leukaemias that include CLL within their lineage differ because of when they originate in the maturation process. The further along they are in the maturation process, the less acute they are, which we also see with the IgHV split in CLL identified by Prof Terry Hamblin. By the time B-lymphocytes have reached the stage of maturity that results in CLL, you've only got the plasma cell and B-memory cell phases left after you reach the mutated IgVH stage. Still, the improved understanding of the B-cell maturation process and how it can be redirected may provide a useful spin-off that will help with CLL treatment.

    Neil

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