Acute Myeloid Leukemia (AML) is a malignant clonal hematological neoplasm characterized by the infiltration of blasts, resulting in the failure of mature blood cells in the bone marrow and peripheral blood. Different genetic alterations have been reported in AML. Mutations in the TP53 gene are associated with adverse prognosis in AML, leading to reduced patient survival.

In this study, we investigated variants in the coding region of the TP53 gene in AML patients in Amazonas, Brazil, focusing on clinical epidemiological aspects and pathogenicity.

Bone marrow sample was collected from AML patients. The RNA extraction and complementary DNA synthesis were performed. The TP53 exons 2 to 11 were amplified, and nucleotide sequencing was performed by the Sanger method. Hematological data from the patients were also evaluated using peripheral blood.

The study included 25 patients diagnosed with AML, 19 cases de novo, 4 secondary and 2 relapsed AML. Here, 17 (68%) patients were female, the average age was 50.20 years ± 18.30. Hematological parameters showed erythropenia with a red blood cell count of 2.89 (2.355-3.245), thrombocytopenia with 20,000 (13,500-63,000), and leukocytosis with 14,000 (4,385-29,120). Pathogenic variants were predominantly identified in exon 4, also was found in the exons 3, 5, 7, 8, 10 and 11. A total of 47 variants was identified at 25 patients, including multiple hits. Nine variants were classified by CancerVar as pathogenic (L32Q, M43K, A119D, D147N, D181N, R248Q, E271D, P278L and K372N), six as uncertain significance (N29D, Q38H, P72R, W91G, R213R and K357M), as benign (F52V), and 4 variants were not found in the database (L44M, Q51Pfs, P79T and L129Ifs). Additionally, 2 silent variants and 3 frameshift variants were identified.

AML patients commonly present hematological parameters such as erythropenia, thrombocytopenia, and leukocytosis, corroborating with study. The TP53 gene is frequently mutated in human cancers and present in AML cases (10-20%). In this study, least one alteration was identified in the 25 patients. Variants are prevalent in the DBD region and corroborates with the study findings. Mutations in the DBD region can confer loss of function (LOF), attributing a deleterious gain of function (GOF) and rendering resistance to standard AML treatment.

The present study presents results that diverge from the current literature in several significant aspects, contradicting previously established data. The TP53 mutations were prevalent in the AML patients from Amazonas state. These findings highlight the need for more in-depth analysis and additional studies to better understand the epidemiological and genetic characteristics of the AML patients.