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.
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:
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.
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, this can be very confusing to me. Stages and all that. I have a question or two for you. On my last bloodwork , I had 1 percent Blast cell count. Is this common to have a Blast count with CLL. I thought it is more common with CML OR AML? Can this be an indication that I may have two Leukemias at the same time( I know very rare but possible). Or since this is so low of a percentage and the first time I have ever seen it on my bloodwork a false positive? Your thoughts? STAY STRONG J.R.
All CLL patients have a percentage of cells that appear less mature by morphology called prolymphs.
Analysers and inexperienced morphologists sometimes classify them as blast cells which they are not. As with all your counts, keep an eye on the trend.
Nothing really, that's sometimes down to the skill of the person making the blood smear as they are just broken lymphocytes. CLL cells appear to be quite fragile compared to other white blood cells.
I heard that the number of smudge cells --over 30% is a positive sign in terms of treatment. As you stated "fragile" so it is easier to get rid of them.
No, not easier to get rid of them. It's just an artifact produced by making the blood smear. As it's an artifact they are not an indicator for treatment when seen at any level.
Seems like PSP52 has read, as I have, that a higher incidence of smudge cells being present is a good prognostic indicator. Here is the relevant paper: ncbi.nlm.nih.gov/m/pubmed/2...
Sorry, I think that's a very weak paper and does not show cause and effect.
I would be more impressed if they had done repeated smears on the same sample, all made by the same person (or automated ones) and then showed that the number of smudge cells was the same each time and only then could it be correlated it to progression, stage etc etc.
As I said, the smudge cells are an artifact produced by the spreading of the smear and are very dependent on technique.
Neil, I shared this with Jm. And wanted to share with you as well. MDA'S response to the abnormal Blast Count-"The blasts are nothing to be concerned about. Every now and then they will sneak out of the bone marrow and show up in the blood. We do not see CLL transform into CML or AML, and it is highly rare to see a patient develop 2 different types of leukemia (for example, CLL and CML). Your counts are otherwise very good with a mildly high but stable WBC.
I hope this answers your question - let us know if there's anything else you need.
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