Malignant Regenerative Cells Induced by Chemotherapy: A Possible Cause of AML Relapse

By Riya Gandhi ‘22

leukemia.jpg

Figure 1. Acute myeloid leukemia progresses far more rapidly than chronic leukemia.

Relapse of acute myeloid leukemia (AML) — or any type of cancer, for that matter — has always posed an enormous challenge to patients and physicians alike. However, a recent study conducted by researchers at McMaster University has found that it is not predominantly leukemic stem cells that induce such recurrence but rather leukemic-regenerating cells that arise post-chemotherapy.

In this study, researchers took AML xenografts and patient samples and treated them with cytarabine-based chemotherapy to replicate patient remission. When observing the samples, they discovered that leukemic stem cells (LSCs) were depleted due to cell-cycle recruitment; however, it was unclear to the scientists how such relapse in AML could occur due to LSCs. It appeared as though primitive AML cells were vulnerable to annihilation during chemotherapy. Further investigation of these samples post-chemotherapy using in-vivo methodology led to the revelation that leukemic-regenerating cells (LRCs) were emerging and thereby triggering the recurrence of AML. Rather than undergoing regular, healthy hematopoiesis, re-growth of leukemic cells occurred in a more aggressive fashion due to the temporary presence of LRCs, which are molecularly different than LSCs: unlike LSCs, they are responsible for a period during which the body is susceptible to leukemia. As such, the individual is extremely vulnerable to relapse; however, this time, the state of the LSCs differ from that of the LSCs present before chemotherapy was introduced. The researchers also successfully determined that it was mainly cytarabine-based chemotherapy that provoked such aggressive regrowth.

Not only does this discovery add to scientists’ understanding of leukemia, but it also gives physicians and scientists key characteristics by which to foresee or identify relapse. It may ultimately be possible to genetically modify LRCs to slow down or suppress recurrence, thereby improving survival rates for individuals who suffer from AML.

 

References

  1. A. Boyd, et. al., Identification of chemotherapy-induced leukemic-regenerating cells reveals a transient vulnerability of human AML recurrence. Cancer Cell 34 (2018). doi: https://doi.org/10.1016/j.ccell.2018.08.007.  
  2. Image retrieved from: https://www.pexels.com/photo/left-human-injected-with-hose-on-white-textile-1243364/
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