Affiliation:
1. Laboratorio Genética Molecular Humana, Universidad Simón Bolívar, Venezuela
Abstract
Acute Lymphoblastic Leukemia (ALL) is the most common neoplasm in pediatric age. In recent years, between 15 and 20% of patients failed in their treatments. Knowledge on cytogenetics and molecular biology has an important impact on the determination of the prognosis and the appropriate treatment scheme. In Venezuela there is limited knowledge regarding the molecular genetics of this onco-hematological alteration. The aim of this work was to evaluate the most frequent genetic alterations in Venezuelan patients with a clinical diagnosis of acute lymphoblastic leukemia. A cross-sectional, descriptive and prospective study was carried out from 2006 to 2014, in which the translocations ETV6/RUNX1, MLL/AF4, TCF3/PBX1, BCR/ABL1, as well as mutations in the PAX5 and FLT3 genes were evaluated through the use of different types of PCR. One hundred and thirty patients with a clinical diagnosis of acute lymphocytic leukemia were included in the study. Molecular alterations were identified in 56 patients (43.1%), in which we observed the presence of one or several alterations in conjunction in the same patient. The alterations identified were t(12; 21) (11.5%), t(4; 11) (8.5%), t(1; 19) (10%), t(9; 22) (20.8%), ITD-FLT3 (14.8%), P80S mutation (4.2%) and S77del (4.2%) in the PAX5 gene. The prevalence of BCR/ABL is one of the highest described so far in cases of ALL where most of the population is made up of pediatric patients. These results represent the first molecular study of ALL in Venezuela, laying the foundations for the diagnosis and monitoring of the disease in its population.
Key words: Acute Lymphoblastic Leukemia; Translocations; ETV6/RUNX1; MLL/AF4; TCF3/PBX1; BCR/ABL1; PAX5; FLT3.
Publisher
Sociedad Argentina de Genetica
Subject
Genetics (clinical),Genetics,Applied Microbiology and Biotechnology,Biotechnology
Reference34 articles.
1. Abdullaev F., Rivera Luna R., Roitenburd Belacortu V., Espinosa Aguirre J. (2000) Pattern of childhood cancer mortality in Mexico. Arch. Med. Res. 31: 526-531.
2. Armstrong S.A., Kung A.L., Mabon M.E., Silverman L.B., Stam R.W., den Boer M.L. (2003) Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell. 3 (2): 173-183.
3. Armstrong S.A., Staunton J.E., Silverman L.B., Pieters R., den Boer M.L. (2002) MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat. Genet. 30 (1): 41-7.
4. Ayatollahi H., Keramati M.R., Shirdel A., Kooshyar M.M., Raiszadeh M., Shakeri S. (2018) BCR-ABL fusion genes and laboratory findings in patients with chronic myeloid leukemia in northeast Iran.
5. Caspian J. Intern. Med. 9 (1): 65-70. Capote L. (2012) Perfil epidemiológico y control del cáncer en Venezuela. Academia Nacional de Medicina 4 (44).