Profiling FLT3 Mutations in Mexican Acute Myeloid Leukemia Pediatric Patients: Impact on Overall Survival

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

doi:10.3389/fped.2020.00586

Cited by 8 publications

(13 citation statements)

References 64 publications

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“…Demographic, clinical, and the main biological characteristics of the patients were previously reported ( 17 ). Fifty-five percent of the patients were male.…”

Section: Resultsmentioning

confidence: 99%

“…Data were collected from medical charts, including sex, age, peripheral white blood cell count, percentage of bone marrow blasts at diagnosis, FAB (French-American-British) classification, and treatment protocol. The clinical features of the analyzed patients had been previously reported in Molina et al ( 17 ).…”

Section: Methodsmentioning

confidence: 94%

“…The statistical analysis was performed as described previously ( 17 ). For dichotomic variables, chi-square or two-sided’ Fisher’s exact test was used to compare proportions among different groups.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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BackgroundIn 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 StudyTo 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 MethodsDNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing of CEBPA was performed in 80 patients.ResultsCEBPA 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 (CEBPABI) mutations were identified in five patients. M2 subtype was the most common in CEBPA positive patients (CEBPAPOS) (p = 0.009); 50% of the CEBPAPOS patients had a WBC count > 100,000 at diagnosis (p = 0.004). OS > 1 year was significantly better in CEBPA negative (CEBPANEG) patients (p = 0.0001). CEBPAPOS patients (either bi- or monoallelic) had a significantly lower OS (p = 0.002). Concurrent mutations in FLT3, CSF3R, and WT1 genes were found in CEBPAPOS individuals. Their contribution to poor OS cannot be ruled out.ConclusionCEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of CEBPAPOS 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.

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“…Demographic, clinical, and the main biological characteristics of the patients were previously reported ( 17 ). Fifty-five percent of the patients were male.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 94%

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

et al. 2022

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“…Similar relationships were observed also in some previous studies 16 , 29 , 34 . Moreover, Molina Garay et al demonstrated that patients with the FLT3 -ITD mutation characterized with significantly shorter lifespan as compared to patients lacking the FLT3 -ITD mutation or with a mutation in the tyrosine kinase domain ( FLT3 -TKD) 36 .…”

Section: Discussionmentioning

confidence: 99%

TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia

Dratwa

Wysoczańska

Butrym

et al. 2021

Sci Rep

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Acute myeloid leukaemia (AML) is a neoplasm of immature myeloid cells characterized by various cytogenetic alterations. The present study showed that in addition to the FLT3-ITD and NPM1 mutation status, telomere length (TL) and telomerase reverse transcriptase (TERT) gene polymorphisms may affect risk and overall survival (OS) in AML. TL was longer in healthy controls than in AML patients and positively correlated with age in the patients, but not in healthy subjects. TL was found to be independently affected by the presence of the FLT3-ITD mutation. As for the TERT gene polymorphism, AML patients with the TERT rs2853669 CC genotype were characterized by significantly shorter OS than patients carrying the T allele. Another observation in our study is the difference in TL and OS in patients belonging to various risk stratification groups related to the FLT3-ITD and NPM1 mutation status. Patients with adverse risk classification (mutation in FLT3-ITD and lack of mutation in NPM1) presented with the shortest telomeres and significantly worse OS. In conclusion, OS of AML patients appears to be affected by TERT gene variability and TL in addition to other well-established factors such as age, WBC count, or FLT3-ITD and NPM1 mutation status.

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“…In contrast, mutations in FLT3-ITD, DNMT3A, NPM1 , and IDH2 were underrepresented in Hispanics ( Gomez-Arteaga et al 2020 ). However, mutated FLT3 was recently shown to have a negative impact on outcomes in Mexican children ( Molina Garay et al 2020 ).…”

Section: Acute Leukemiasmentioning

confidence: 99%

Blood cancer health disparities in the United States Hispanic population

Bencomo‐Alvarez

Rubio

Gonzalez

et al. 2021

Cold Spring Harb Mol Case Stud

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Cancer is a challenging, multifaceted disease that involves a combination of biological and non-biological factors. Aside from COVID-19, cancer is the second leading cause of death in the United States (U.S.), and the first among Hispanic Americans. The Hispanic population is the largest minority group in the U.S., which is rapidly growing in size. Unfortunately, U.S. Hispanics and other minority groups experience many different health disparities, resulting in poor survival outcomes and a reduced quality of life. Factors such as genomic mutations, lower socioeconomic status, lack of education, reduced access to health care, comorbidities, and environmental factors all contribute to these health care inequalities. In the context of blood cancer health disparities, Hispanic patients are often diagnosed at a younger age and have worse outcomes compared with non-Hispanic individuals. In the present article, we highlight the existing knowledge about cancer health disparities in the Hispanic population, with a focus on chronic and acute leukemia. In our experience at the U.S./Mexico border, analysis of several different blood cancers demonstrated that younger Hispanic patients with acute lymphoid or myeloid leukemia have higher incidence rates and worse prognoses. A combined approach, involving improved health care access and better knowledge of the underlying factors, will allow for more timely diagnoses and the development of intervention strategies aimed at reducing or eliminating the disparities.

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Profiling FLT3 Mutations in Mexican Acute Myeloid Leukemia Pediatric Patients: Impact on Overall Survival

Cited by 8 publications

References 64 publications

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

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

TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia

Blood cancer health disparities in the United States Hispanic population

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