AUTHOR=Molina Garay Carolina , Carrillo Sánchez Karol , Flores Lagunes Luis Leonardo , Jiménez Olivares Marco , Muñoz Rivas Anallely , Villegas Torres Beatríz Eugenia , Flores Aguilar Hilario , Núñez Enríquez Juan Carlos , Jiménez Hernández Elva , Bekker Méndez Vilma Carolina , Torres Nava José Refugio , Flores Lujano Janet , Martín Trejo Jorge Alfonso , Mata Rocha Minerva , Medina Sansón Aurora , Espinoza Hernández Laura Eugenia , Peñaloza Gonzalez José Gabriel , Espinosa Elizondo Rosa Martha , Flores Villegas Luz Victoria , Amador Sanchez Raquel , Pérez Saldívar María Luisa , Sepúlveda Robles Omar Alejandro , Rosas Vargas Haydeé , Jiménez Morales Silvia , Galindo Delgado Patricia , Mejía Aranguré Juan Manuel , Alaez Verson Carmen 

TITLE=Mutational Landscape of CEBPA in Mexican Pediatric Acute Myeloid Leukemia Patients: Prognostic Implications

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.899742

DOI=10.3389/fped.2022.899742

ISSN=2296-2360

ABSTRACT=<sec><title>Background</title><p>In Mexico, the incidence of acute myeloid leukemia (AML) has increased in the last few years. Mortality is higher than in developed countries, even though the same chemotherapy protocols are used. CCAAT Enhancer Binding Protein Alpha (<italic>CEBPA</italic>) mutations are recurrent in AML, influence prognosis, and help to define treatment strategies. <italic>CEBPA</italic> mutational profiles and their clinical implications have not been evaluated in Mexican pediatric AML patients.</p></sec><sec><title>Aim of the Study</title><p>To identify the mutational landscape of the <italic>CEBPA</italic> gene in pediatric patients with <italic>de novo</italic> AML and assess its influence on clinical features and overall survival (OS).</p></sec><sec><title>Materials and Methods</title><p>DNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing of <italic>CEBPA</italic> was performed in 80 patients.</p></sec><sec><title>Results</title><p><italic>CEBPA</italic> was mutated in 12.5% (10/80) of patients. Frameshifts at the N-terminal region were the most common mutations 57.14% (8/14). <italic>CEBPA</italic> biallelic (<italic>CEBPA</italic><sup>BI</sup>) mutations were identified in five patients. M2 subtype was the most common in <italic>CEBPA</italic> positive patients (<italic>CEBPA</italic><sup>POS</sup>) (<italic>p</italic> = 0.009); 50% of the <italic>CEBPA</italic><sup>POS</sup> patients had a WBC count &gt; 100,000 at diagnosis (<italic>p</italic> = 0.004). OS &gt; 1 year was significantly better in <italic>CEBPA</italic> negative (<italic>CEBPA</italic><sup>NEG</sup>) patients (<italic>p</italic> = 0.0001). <italic>CEBPA</italic><sup>POS</sup> patients (either bi- or monoallelic) had a significantly lower OS (<italic>p</italic> = 0.002). Concurrent mutations in <italic>FLT3</italic>, <italic>CSF3R</italic>, and <italic>WT1</italic> genes were found in <italic>CEBPA</italic><sup>POS</sup> individuals. Their contribution to poor OS cannot be ruled out.</p></sec><sec><title>Conclusion</title><p>CEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of <italic>CEBPA</italic><sup>POS</sup> was in the range reported for pediatric AML (4.5–15%). <italic>CEBPA</italic> mutations showed a negative impact on OS as opposed to the results of other studies.</p></sec>