Acute Myeloid Leukemia: Stem Cell Analysis Transforms Treatment

Rapid screening of the drug response on the stem cells of patients suffering from acute myeloid leukemia is a major prognostic factor for relapses and may make it possible to individualize the treatment of the patient.

In acute myeloid leukemia, direct analysis of the susceptibility of leukemic stem cells to drugs may explain very early why some treatments do not work and why promising early therapeutic results are not maintained.

In this high-throughput gene sequencing study, researchers have shown that the genes expressed in leukemic stem cells can be used to determine resistance or sensitivity to treatment, and that these genes are very different from those expressed by blasts (cells currently targeted by chemotherapy). The examination also objected to differences in sensitivity profile between patients.

It thus becomes possible to know from the beginning of the disease the drugs that will target both the diseased stem cells and the blasts and to individualize the treatment, in order to radically treat the disease and to prevent patients from relapsing. These results were presented at the 60th Annual Congress of the American Society of Hematology in San Diego.

A serious form of leukemia

Acute myeloid leukemia (AML) is a serious form of leukemia that affects certain hematopoietic cells (cells that cause the formation of blood elements). In this disease, some cells, early precursors of the bone marrow, that usually develop into white blood cells do not mature properly.

These cells remain blocked as primitive cells, called "blasts", unable to differentiate further and evolve to normal blood cells. These can accumulate and smother the bone marrow, causing a decrease in white blood cells, which reduces the ability to fight infections, as well as a decrease in platelets, which poses a risk of hemorrhage.

Different sensitivities according to the cells

The researchers found that the genetic susceptibility patterns of stem cells and acute myeloid leukemia blasts diverged and that these profiles also differed from one patient to another.

Thus, it appears that blasts most often respond to the drugs most commonly used to treat patients, which explains the initial regression of the disease, but none of these drugs is effective against leukemia stem cells, which explains perfectly why the disease relapses, even after elimination of blasts.

The researchers found 12 drugs belonging to eight classes that seemed to preferentially target leukemia stem cells relative to blasts. Many of them are most often not used in patients with this type of blood cancer, which opens up immediate prospects for improving treatment.

A study with double relaxation

This study examined the response to drugs in stem cells and blasts collected from patients with acute myeloid leukemia. The information was analyzed using high-throughput gene sequencing, a method for rapidly evaluating and testing genes in many samples.

In an in vitro study, the researchers then compared the drug susceptibility of blast and stem cell populations from the same six patients. In doing so, they tested a customized panel of drugs, targeted agents and drug combinations on the cells, and performed genetic analyzes for 194 mutations. The panel included both FDA-approved drugs and experimental drugs.

A major breakthrough

The differentiated characteristics of drug sensitivity observed by high-throughput gene sequencing in stem cells and blasts of acute myeloid leukemia allow scientists to hope that individualized therapeutic approaches could be developed against acute myeloid leukemia. In perspective, it is the improvement of treatment results for people with this serious form of blood cancer.

Video: The AML genomes: Mutations in four dimensions (January 2020).