A study reveals the causes of the increase in chronic hematological diseases

An investigation led by the October 12 of October of the Community of Madrid in collaboration with the Severo Ochoa Molecular Biology Centerhas discovered the reason why the risk of suffering is increased Chronic myeloproliferative neoplasmsa group of diseases that affect the functioning of the bone marrow. It is the increase in a protein that weakens the immune responses of the body. Is called PD-L1 And its increase triggers the development of the disease, once the genetic mutation that causes these pathologies is acquired. The finding opens the door to the application of anti PD-L1 drugs, already used in other tumors, which could stop the progression of these diseases to other potentially mortal ones such as the leukemia o to mielofibrosis.

Although more than a decade ago it was already described that the genetic variant Haplootype 46/1 JAK2 Explain almost 30 percent of the population’s risk to suffer chronic myeloproliferative neoplasms, so far no one had managed to explain why. Gonzalo Carreño, Hematologist, Researcher at the 12 de Octubre Hospital and principal researcher and author of the work The Jak2 46/1 Haplotype Influences PD-L1 Expressionpublished in the magazine Bloodexplains the finding: “We studied DNA and saw that a genetic variant, the Haplootype 46/1 of JAK2 interacted with the PD-L1 protein, and we saw that the population that has that gene had increased the PD-L1. This protein acts as a brake to the immune responses of the body. This makes, if you have acquired the characteristic mutations of the neoplasm mutations of the neoplasm. disease progress more quickly or more frequently “.

There is the circumstance that, although myeloproliferative neoplasms are a group of Rare diseaseswith a population incidence of 2 cases per 100,000 inhabitants, the 46/1 haplotype of JAK2 It has about 50 percent of the population. The trigger for the development of the disease would be interaction with PD-L1.

Dr. Carreño explains that there are already anti PD-L1 drugs that are used for diseases such as lung cancer or lymphomas. “These drugs are effective and to tolerate very well. When the patient acquires the mutation of the disease, at first it has little tumor load, less symptoms and it may take years to progress to terminal phases, such as acute leukemia or myelofibrosis, which are those that decrease survival and quality of life. This research opens the door to the use of these drugs in these pathologies. We would stop progression, we would improve the prognosis and quality of life of patients, we would reduce the symptoms and complications of the disease “.

For its part, Dr. Miguel Manzanares, CBM researcher and one of the study authorshighlights: “This work is an example of how basic research in molecular biology can have a direct impact on the understanding and possible treatment of human diseases. We have identified a functional genetic interaction that not only explains a clinical risk, but also opens new therapeutic perspectives,”.

Chronic myeloproliferative neoplasms are Tumor diseases of the hematopoietic stem cell in which an anomalous proliferation of blood cells occurs. Consequently, patients have many platelets, many red blood cells or bone marrow is fibrous, which have complications such as the increased risk of thrombosis, constitutional symptoms such as weight and sweating loss, itching that are not well controlled and the long complications such as the development of acute leukemia or myelofibrosis.

Researchers warn that it will be necessary to validate these results in animal models and clinical trials before incorporating these treatments into the usual clinical practice. For Dr. Carreño “We are facing a great advance in the knowledge of why these diseases occur and, above all, given an opportunity to look for new therapeutic targets in these patients”.