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ASH 2019: Dr. Neil Kay on how the chronic lymphocytic leukemia (CLL) microenvironment affects blood cell production

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Our blood is composed of many different types of cells including red blood cells, platelets and white blood cells. We need these cells to stay healthy and to avoid infections, but they only live for a short time so they need to be replenished continuously. Hematopoiesis is the process by which our bodies continuously manufacture blood cells, and this process takes place mainly in the bone marrow.

Patient with chronic lymphocytic leukemia (CLL) have reduced immune function and thus are very susceptible to infections and secondary cancers. However, it is not known whether this reduction in immune function is due to:

  • the natural progression of CLL,
  • a consequence of the drugs used to treat CLL, or
  • changes in the bone marrow where immune cells are produced.

At the annual meeting of the American Society of Hematology (ASH) 2019, our own Dr. Brian Koffman interviewed Dr. Neil Kay, a Professor of Medicine and a hematologist at Mayo Clinic, about what happens to hematopoiesis in patients with CLL and how the microenvironment influences it.

The microenvironment is the normal cells, molecules, and blood vessels that surround and feed the cancer cells. The microenvironment can influence how the cancer cells grow and spread. Cancer cells can also change their microenvironment to help them survive. Molecules produced by the cancer cells can affect the normal function of the surrounding tissues such as bone marrow.

The big questions Dr. Kay’s lab has been studying are:

  • In patients with CLL (who have not yet been treated) is hematopoiesis functioning properly?
  • What are the mechanisms that cause disordered hematopoiesis?

Takeaways:

  • In untreated patients with CLL, the bone marrow is not functioning normally
  • It is not explained only by tumor burden (ie, cancer cells physically crowding out normal cells for available space)
  • Certain proteins that turn genes “on” or “off” (transcription factors) that are required for normal hematopoiesis are significantly increased in patients with CLL.
  • The inflammatory molecule tumor necrosis factor (TNF) seems to cause these abnormal increases in certain proteins in the laboratory, and conversely blocking TNF reverses these changes.
  • CLL B cells are always producing TNF, so it is part of microenvironment in CLL that can affect the bone marrow.

Conclusions:

Researchers believe that even in early-stage CLL the bone marrow is not able to produce the immune cells needed to be healthy, and these effects are at least partially due to TNF in the microenvironment. In the future, researchers are interested in studying the potential use of drugs that block TNF to reverse disordered hematopoiesis.

Please enjoy this interview with Dr. Kay from December 2019 at ASH in Orlando, FL.

You can also read their previous paper here: Bone Marrow Hematopoietic Dysfunction in Untreated Chronic Lymphocytic Leukemia Patients

Take care of yourself first.

Ann Liu, PhD