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Scientists identify new genetic variant in a family with acute myeloid leukemia
A rare case of hematological cancer was described based on a child and five other family members; genetic testing prevented transplantation and enabled personalized treatment with remission
Leukemia is the most common type of cancer in children. About 10% are acute myeloid leukemia (AML) – Photo: Freepik
Researchers from USP’s Faculty of Medical Sciences of Ribeirão Preto (FMRP) and the Fleury Group Laboratory followed a rare case of familial acute myeloid leukemia (AML) in a girl of just 6 years old. The research identified five other cases in the same family, all diagnosed in adolescence, as well as two mutations in the CEBPA gene – essential for giving rise to the cells that protect against bacterial and fungal infections.
The case was described in an article published in the international journal Hematology, Transfusion and Cell Therapy and reported, in an unprecedented way, a new hereditary variant of the CEBPA gene. According to hematologist Lorena Lobo Figueiredo Pontes, knowledge of genetic alterations in this type of leukemia is a decisive factor in whether or not a patient is referred for a bone marrow transplant.
“The alterations associated with a more favorable prognosis, which can initially avoid this therapy, and those that characterize the most aggressive leukemias, which require transplantation very quickly, are known. Considering transplantation’s complexity, risks, and costs, this knowledge is fundamental,” she says. Lorena is the coordinator of the International Consortium on Acute Leukemia, a global initiative of the American Society of Hematology, and a professor in the Department of Medical Imaging, Hematology, and Clinical Oncology at FMRP.
AML is a neoplasm of the blood system caused by the accumulation of stem cells in the bone marrow, where stem cells are produced. The disease known as “blood cancer” occurs when stem cells, also called immature or precursor cells, lose their ability to differentiate into specific cells and gain survival and expansion advantages, rapidly occupying the bone marrow and preventing the formation of normal cells.
Lorena Pontes is a professor in the Division of Hematology, Hemotherapy and Cell Therapy – Photo: RIO / FMRP
To arrive at the case described in the study, the researchers conducted a long-term follow-up of 187 patients diagnosed with acute myeloid leukemia. Of the 187 patients, 18 had a variant in the CEBPA gene. “The CEBPA gene encodes an essential protein for the differentiation of myeloid cells that give rise to neutrophils in our peripheral blood, i.e., the cells that protect us from bacterial and fungal infections,” the hematologist explains.
Mutations in this gene can be detected in around 5% to 15% of cases, but gene sequencing tests are not available in the SUS (Unified Health System) for patients with acute leukemia. Cases become even more delicate when they involve an entire family with germline mutations, i.e. mutations that can be passed on to offspring.
Lorena explains that the great difficulty in these cases is in obtaining research for mutations in CEBPA and other genes associated with myeloid neoplasms such as AML.
At USP’s Hospital das Clínicas in Ribeirão Preto, she says, it was only possible to carry out the research on patients included in the investigator’s clinical studies with research funding.
Gene sequencing tests are not available in the SUS for patients with acute leukemia, nor for family members. It is hoped that, through scientific dissemination, health management in the country will become aware of these demands”
Histological slide of bone marrow shows an accumulation of immature blood cells, preventing the growth of white blood cells – Image: Makysm / Wikimedia Commons
Variations in the gene
CEBPA is one of the genes that can show a variation in somatic cells and lead to the development of AML at some stage in life, but it can also be germline mutated, present in the person from birth, and can be transmitted hereditarily.
The study highlighted that germline mutations in CEBPA not only predispose to the development of acute myeloid leukemia but also influence the additional mutations that arise during the disease’s evolution. He also emphasizes the importance of genetic testing in families with a history of hematological cancer, both to guide therapeutic options – such as bone marrow transplantation – and to identify and avoid donors from the same family.
“In our investigation, five familial cases of AML were identified, including the compatible sister for the bone marrow transplant who had the same mutation, which was useful in contraindicating the procedure and directing the patient to treatment with chemotherapy only,” says Lorena.
The patient’s treatment followed standard pediatric chemotherapy protocols and resulted in complete remission without the need for a bone marrow transplant. Two years after treatment, the patient remains healthy and has no signs of relapse.
“The early identification of genetic mutations such as this is essential to provide patients and their families with adequate care. Studies like this help build the knowledge needed for faster diagnosis and more effective treatments in the future,” says Maria de Lourdes Chauffaille, co-author of the study and medical consultant at Grupo Fleury.
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Genetic research is very relevant for the USP professor because the patients don’t have any other disorders that raise doubts about a hereditary disease. For this reason, cases of AML in childhood and in patients with a strong family history of the same condition merit genetic research. “In addition, knowledge of the mutation profile at diagnosis allows personalized monitoring of the response to treatment using highly sensitive techniques. The case description also adds a new variant to the world’s genetic databases, optimizing molecular diagnosis for other cases,” adds Lorena Pontes.
The study Familial acute myeloid leukemia due to a novel germline CEBPA pathogenic variant – a case report is available at this link.
More information: lorenafigdo@usp.br, with Lorena Lobo Figueiredo Pontes
*With information from Fleury Group’s Communications Office
English version: Nexus Traduções
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A reprodução de matérias e fotografias é livre mediante a citação do Jornal da USP e do autor. No caso dos arquivos de áudio, deverão constar dos créditos a Rádio USP e, em sendo explicitados, os autores. Para uso de arquivos de vídeo, esses créditos deverão mencionar a TV USP e, caso estejam explicitados, os autores. Fotos devem ser creditadas como USP Imagens e o nome do fotógrafo.