Leukemia Article

[ASUgrad2021]

I thought I would share this interesting study I came across.

hindawi.com/journals/omcl/2...

[AussieNeil Administrator]

Sorry, but that article is about Acute Myeloid Leukaemia and such papers are usually not relevant to CLL* - Chronic Lymphocytic Leukaemia. There are about 200 different blood cancers, so it's important to find research which is closely related to CLL for it to be most helpful.

If you look at the accompanying diagram of hematopoesis - how our blood cells are made, you'll see that there are two primary progenitor stem cells - myeloid to the left and lymphoid to the right. CLL is actually characterised as a Non-Hodgkin's B cell Lymphoma, so it belongs in the bottom right of the diagram. Leukaemias/Lymphomas are also divided into acute and chronic and CLL is one of the approximately 20 chronic lymphomas.

Per the article you referenced, section 4. Acute Myeloid Leukaemia

AML develops from a common myeloid progenitor, a cell which would physiologically differentiate to form monocytes, granulocytes, platelets, and erythrocytes in the bone marrow. (You can see these on the right side of the diagram)

One of the traps when it comes to finding CLL related research is that much of the research relies on the establishment of immortal cell lines; cells that can be grown, characterised and sold for research to laboratories around the world. This is what enables independent validation of research. Quick research to get a paper published is easily done with fast growing cell lines that you can observe under a microscope - in vitro research. Despite CLL being the most common adult leukaemia/lymphoma, you don't tend to find as much research on it because CLL is not immortal, so it's been difficult to develop cell lines for research.

* That said, there are a few mentions of CLL in section 6, where the authors note "altered GSH content might be a common property of primary hematopoietic malignant tissues." The full paragraph is; "Primitive hematopoietic stem and progenitor cells reside within the bone marrow and express the CD34 surface antigen [73, 74]. Moreover, primitive AML cells also generally express CD34 and are more resistant to chemotherapy [74, 75]. A recent study by Pei et al. evaluates the characteristics of primary CD34+ cells derived from patients with AML in comparison to normal CD34+ controls [76]. This is consistent with the finding that CLL cells have elevated levels of reactive oxygen species (ROS) compared to normal controls [77]. Taken together, this suggests that altered GSH content might be a common property of primary hematopoietic malignant tissues."

If you look through PubMed, you can find research papers such as "Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide"

pubmed.ncbi.nlm.nih.gov/375...

and "Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism,” Blood, vol. 112, no. 5, pp. 1912–1922, 2008

.ashpublications.org/blood/a...

but these are with respect to older, chemotherapy treatments fludarabine and cyclophosphamide, the FC in FCR.

Neil

CLL is a lymphoid blood cancer (right of diagram), not a myeloid blood cancer (left)

[SeymourB]

ASUgrad2021 -

There's been research on ROS's and CLL, such as:

ncbi.nlm.nih.gov/pmc/articl...

Higher levels of reactive oxygen species are associated with anergy in chronic lymphocytic leukemia

Haematologica. 2015 Jul; 100(7): e265–e268.

Anergy means that the B-cell does not respond to antigens.

It's tempting to leap from cellular dynamic studies to some therapeutic change. The questions that need to be answered have to do with effective dosage reaching the right part of the right cells, which is a very tough nut to crack.

I would also note that ROS's are vital in immune defense against pathogens. I find it interesting that this is yet another example how a normal, even vital processes in one area of the body can be abnormal in another.

ROS's should also not be confused with ROUS's, which are Rodents of Unusual Size who inhabit the Fire Swamp.😅

=seymour=