Dataset Information

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

ABSTRACT:

Background

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 (CEBPA) mutations are recurrent in AML, influence prognosis, and help to define treatment strategies. CEBPA mutational profiles and their clinical implications have not been evaluated in Mexican pediatric AML patients.

Aim of the study

To identify the mutational landscape of the CEBPA gene in pediatric patients with de novo AML and assess its influence on clinical features and overall survival (OS).

Materials and methods

DNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing of CEBPA was performed in 80 patients.

Results

CEBPA was mutated in 12.5% (10/80) of patients. Frameshifts at the N-terminal region were the most common mutations 57.14% (8/14). CEBPA biallelic (CEBPA ^BI) mutations were identified in five patients. M2 subtype was the most common in CEBPA positive patients (CEBPA ^POS) (p = 0.009); 50% of the CEBPA ^POS patients had a WBC count > 100,000 at diagnosis (p = 0.004). OS > 1 year was significantly better in CEBPA negative (CEBPA ^NEG) patients (p = 0.0001). CEBPA ^POS patients (either bi- or monoallelic) had a significantly lower OS (p = 0.002). Concurrent mutations in FLT3, CSF3R, and WT1 genes were found in CEBPA ^POS individuals. Their contribution to poor OS cannot be ruled out.

Conclusion

CEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of CEBPA ^POS was in the range reported for pediatric AML (4.5-15%). CEBPA mutations showed a negative impact on OS as opposed to the results of other studies.

SUBMITTER: Molina Garay C

PROVIDER: S-EPMC9367218 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Mutational Landscape of <i>CEBPA</i> in Mexican Pediatric Acute Myeloid Leukemia Patients: Prognostic Implications.

Molina Garay Carolina C Carrillo Sánchez Karol K Flores Lagunes Luis Leonardo LL Jiménez Olivares Marco M Muñoz Rivas Anallely A Villegas Torres Beatríz Eugenia BE Flores Aguilar Hilario H Núñez Enríquez Juan Carlos JC Jiménez Hernández Elva E Bekker Méndez Vilma Carolina VC Torres Nava José Refugio JR Flores Lujano Janet J Martín Trejo Jorge Alfonso JA Mata Rocha Minerva M Medina Sansón Aurora A Espinoza Hernández Laura Eugenia LE Peñaloza Gonzalez José Gabriel JG Espinosa Elizondo Rosa Martha RM Flores Villegas Luz Victoria LV Amador Sanchez Raquel R Pérez Saldívar María Luisa ML Sepúlveda Robles Omar Alejandro OA Rosas Vargas Haydeé H Jiménez Morales Silvia S Galindo Delgado Patricia P Mejía Aranguré Juan Manuel JM Alaez Verson Carmen C

Frontiers in pediatrics 20220711

<h4>Background</h4>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 (<i>CEBPA</i>) mutations are recurrent in AML, influence prognosis, and help to define treatment strategies. <i>CEBPA</i> mutational profiles and their clinical implications have not been evaluated in Mexican pediatric AML patients.<h4>Aim of the ...[more]

PMID: 35967564

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