Detecting alterations in some proteins would avoid chemotherapy in 85% of patients with acute myeloid leukemia

Acute myeloid leukemia is a very common tumor with a high mortality rate.. Just over 50% of young adults survive after diagnosis, a figure that drops to less than 10% of those over 65 years of age.. “We have to be able to be precise in the treatments that we give to these patients, as is done in other tumors, such as in the breast, where biomarkers are used as a clue to adjust which therapy will respond best,” explains María Linares, researcher of the Hospital 12 de Octubre and the Complutense University of Madrid.

Up to 85% of patients could avoid the first line of treatment with chemotherapy and its side effects, opting for other more effective therapies if the alterations of some proteins will be determined to detect those who do not respond to standard therapy. “The current option is based mainly on the administration of cytarabine [an antineoplastic used in this type of hematological tumors discovered in 1970] along with other drugs,” explains Linares..

But the researcher qualifies that “although it is an effective drug, the vast majority of patients develop resistance, and very few of them survive in the long term. By being able to predict which patients are not going to respond, we would avoid chemotherapy and its side effects, such as anemia, thrombocytopenia and all the alterations that occur in blood cells”.

The prevalence of acute myeloid leukemia is high. Every year between three and four new cases of this blood tumor are diagnosed for every 100,000 inhabitants, according to the Spanish Association of People Affected by Lymphoma, Myeloma and Leukemia (AEAL).. The figure rises to 20 when it comes to people over 65, points out Linares. Since cancer cells spread rapidly through the blood it is an aggressive cancer.. This type of leukemia represents 40% of all leukemias, point out from the Josep Carreras Foundation.

Linares's team has published a study in Leukemia, a scientific publication of the Nature group, an investigation that paves the way for precision therapies in acute myeloid leukemia. Using cell models and patient samples, they have observed that proteins involved in gene processing (called splicing) are involved in cytarabine resistance..

“What we have done has been to take samples from patients who were resistant to treatment or not and compare them. So we have carried out studies at the messenger RNA level and discovered that mRNA splicing and the phosphorylation of serine-arginine (SR)-rich proteins were altered during cytarabine resistance,” summarizes the researcher..

The study is signed by his team and the main authors María Luz Morales and Roberto García-Vicente, both from the Research Institute of the Hospital 12 de Octubre i+12. Its objective is to put on the table an option within the range of personalized medicine available and design new treatments for refractory patients..

“We have developed a simple form, in the form of a smear, with which we could obtain this information from patients diagnosed with this type of leukemia,” explains Linares.. “Only a small amount of sample is needed. You just put a small droplet on a glass. We then stain the antibodies because they specifically recognize the proteins.”.

The October 12 researcher explains that they have series with samples of between 60-70 patients who could be classified as responders or not to standard treatment.. In the hospital it could be used “as a response biomarker”.

This same work has a second practical part, because they have also evaluated the efficacy and toxicity of possible new treatments.. Once it is known that there will be no response to the usual first line, a solution must be found