Search

Objetivo: el objetivo general de este trabajo fue determinar las características clínicas y citogenéticas de una serie de pacientes con diagnóstico de leucemia promielocítica aguda (LPA) atendidos en un hospital universitario de la ciudad de Medellín, Colombia entre los años 2012 y 2020. Materiales y métodos: se realizó un estudio descriptivo retrospectivo de todos los pacientes mayores de 15 años con diagnóstico confirmado de LPA, atendidos en el Hospital Universitario San Vicente Fundación (HUSVF) de la ciudad de Medellín, Colombia entre los años 2012 a 2020. Se revisaron los registros CIE 10 para identificar los posibles casos; posteriormente se revisaron las historias clínicas completas de los pacientes y se incluyeron aquellos con diagnóstico confirmado por cariotipo, FISH o PCR. Se realizó un análisis univariado y bivariado con el software estadístico SPSS(IBM)®, considerando la diferencia como estadísticamente significativa si p

Introducción. La leucemia promielocítica aguda (LPA) es un subtipo poco frecuente de leucemia mieloide aguda (LMA), que se caracteriza por un comportamiento clínico particularmente agresivo, y en ausencia de tratamiento, su curso generalmente es fatal. El objetivo de este trabajo fue determinar las características clínicas y citogenéticas de una cohorte de pacientes con LPA, con la finalidad de evaluar su relación con las complicaciones, el pronóstico y el desenlace de estos pacientes. Metodología. Se realizó un estudio observacional, descriptivo, retrospectivo de los pacientes mayores de 15 años con diagnóstico de LPA, atendidos en el Hospital Universitario San Vicente Fundación, entre los años 2012 a 2020. Resultados. Un total de 32 pacientes fueron incluidos. La edad media del diagnóstico fue 37 años. El 84,4% de los pacientes tenía la traslocación (15;17) en el cariotipo, y el 93,75% tenían FISH positivo. El 12,5% de los casos tenían cariotipo complejo. La mortalidad en los primeros 30 días fue del 15,6%, siendo el sangrado la causa de muerte más frecuente. Todos los pacientes que sobrevivieron alcanzaron la remisión completa (84,3%). En un promedio de seguimiento de 24 meses, el 14,8% de los casos recayeron. En el análisis bivariado se encontró relación entre sexo masculino y tener cariotipo complejo (p=0,015). No se encontró relación entre cariotipo complejo y mortalidad temprana (p=0,358), tampoco entre cariotipocomplejo y recaída (p=0,052). Conclusiones. Se presentan las características clínicas y citogenéticas de una cohorte de pacientes con LPA en Colombia. El sangrado en el sistema nervioso central fue la principal causa de mortalidad temprana, todos los pacientes que sobrevivieron alcanzaron la remisión completa con la terapia de inducción. Las tasas de mortalidad, remisión completa y recaída fueron similares a las reportadas por otras series latinoamericanas, pero inferiores a estudios provenientes de países europeos. Contrario a lo reportado en otros estudios, no se encontró relación entre el cariotipo complejo y la mortalidad temprana o recaída.

Mutations in the BCR-ABL1 tyrosine kinase domain mutations, are one of the principal mechanisms associated with tyrosine kinase inhibitors (TKI) resistance in patients with chronic myeloid leukaemia (CML).Objectives: To determine the type and frequency of mutations in the tyrosine kinase domain of the BCR-ABL1 gene associated with failure to respond to treatment with Imatinib and Imatinib in patients with CMK, and to correlate the mutation profile with the clinical and demographic variables, as well as the cytogenetic and molecular response.Materials and methods: A descriptive prospective study was carried out on patients with CML treated with Imatinib. Karyotyping and analysis of the BCR-ABL1 domain mutations were performed on the patients using nested PCR.Results: Four types of mutations were found in the 23 patients studied, of which two of them were the E225 mutation, one with the H396P mutation, another with a double mutation L387L and T389P. Both the E255K mutation located in the P-loop region, and H396P mutation in the A-loop region, are associated with a poor prognosis. The T389P mutation located within A-loop region has not been reported in any of the databases.Conclusions: Four mutations were found in the tyrosine kinase domain (E255K, H396P, L387L and T389P) were found in this study. These findings provide valuable information and as a guideline to help make treatment decisions. It is important to point out that this analytical study on mutations of the BCR-ABL domain is the first one carried out in the country and, specifically, in a tri-ethnic population.

Resumen Objetivo Analizar la metilacion en los promotores de los genes CDKN2B y DBC1 en muestras de pacientes con leucemia linfoblastica aguda (LLA), leucemia mieloblastica aguda (LMA) y leucemia mieloide cronica (LMC). Ademas, correlacionar el perfil de metilacion de los pacientes con los hallazgos citogeneticos. Materiales y metodos Se evaluaron 56 pacientes con leucemias: 24 con LLA, 16 con LMA y 16 con LMC. El ADN extraido se modifico con bisulfito de sodio. Se realizo un analisis de metilacion en los genes CDKN2B y DBC1 mediante la PCR especifica de metilacion (MS-PCR). Las muestras positivas por la tecnica MS-PCR fueron secuenciadas. Resultados Se encontro una frecuencia total de metilacion del 87,5%. El gen CDKN2B se encontro metilado en el 75% de LLA y de LMC, y del 62% en LMA. El gen DBC1 se encontro metilado en el 96% de LLA, el 94% de LMA y del 68,8% en LMC. El gen mas frecuentemente metilado en todas las muestras fue DBC1 . De los tres tipos de leucemias, la LLA fue la que presento los mayores porcentajes de metilacion. El 62,5% de la muestras tenian metilado ambos genes. Las muestras con cariotipo normal presentaron una alta frecuencia de metilacion de CDKN2B y DBC1 . Conclusiones En este estudio se demostro, por primera vez en pacientes colombianos con leucemias, que la metilacion de los genes CDKN2B y DBC1 es un evento frecuente. Los hallazgos indican que la metilacion de genes supresores de tumores es una via molecular alterna que podria estar relacionada con el desarrollo de neoplasias hematologicas.

Background and Aims FLT3-ITD mutations in acute myeloid leukemia (AML) are associated with a poor prognosis. In Latin America, little epidemiological data exist about these mutations and their influence on clinical evolution and prognosis. Standardization and well-established clinical correlation make FLT3 mutational analysis by molecular methods an invaluable tool to decide among treatment options and to determine AML prognosis. Methods We assessed the prevalence of FLT3-ITD mutations in 138 patients with AML at four hematology referral centers from Mexico and Colombia. Molecular methods based on polymerase chain reaction (PCR) were employed for determining FLT3-ITD status. Results Mutations were present in 28 patients indicating a prevalence of 20.28%. Median age was 47 years (5–96). The FLT3 mutation positive group was older, had higher WBC and hemoglobin values and lower platelet counts but without statistical significance. A not previously described mutation in the FLT3 gene was found in one patient involving a nucleotide exchange of timine for cytosine at the 66608 position. A high mortality was found in the FLT3-mutated group, 67.8 vs. 42.72% in the non-mutated group and median survival was 4.9 months vs. 20.4 months, p = 0.009. A mutated FLT3 did not confer poor prognosis to those with M3 AML. The mutated FLT3 population had poor overall survival (OS) despite hematoprogenitor stem cell transplantation (HSCT). Conclusion Prevalence of FLT3-ITD mutation in AML was present in a proportion comparable to other populations and, when present, was associated with a very poor prognosis.

Objetivo: Determinar si la magnitud del daño en el ADN, se correlaciona con la concentración de malondialdehído (MDA) urinario en individuos expuestos y no expuestos ocupacionalmente a mercurioMetodología: Se evaluaron 64 historias clínicas de individuos pareados por edad, consumo de cigarrillo y alcohol (32 expuestos y 32 referentes) en los que se determinó la concentración urinaria de MDA y se realizó el ensayo cometa (momento de la cola olive, % DNA en cola, tamaño de cola). Se compararon las concentraciones de MDA y las alteraciones en el cometa entre los grupos y se realizó una correlación entre estas variables.Resultados: Hubo mayores concentraciones de MDA en expuestos que en referentes (mediana 1.28 vs 0.51, respectivamente), así como mayores daños en el ensayo cometa (mediana del % ADN en cola: 27.37 vs 0.31; mediana del momento olive de 8.29 vs 0.056; mediana del tamaño de la cola 35 vs 3.0, respectivamente). Sin embargo hubo una mala correlación entre MDA en orina y daño genético (r

Brycon henni, is a native fish from Western Colombia is important as food and in sport fishing, and could be cultured in waters between 18 and 28 degrees C. A previous cytogenetic study in branchial cells indicated different chromosomal complements. Total blood samples were seeded in 4 ml Ham-F12 culture medium, supplemented with 0.5 ml Bovine Fetal Serum and 0.7 ml Phyitohemaglutinin M (Gibco) during 96 hr at 28 degrees C; an antimitotic factor (100 microl Colcemid 10%) was added. Cells were incubated in 10 ml KCl hypotonic solution (0.56%) for 24 min at 37 degrees C, fixed in methanol; acetic acid (3: 1) three times, separated by centrifugations, extended drip, and the chromosomes slides were stained with 5% Giemsa (5%). The best metaphases (6 males and 8 females) were photographed. There was a diploid number of 50 chromosomes: Metacentrics (26M), Submetacentrics (16SM) and Subtelocentrics (8ST). The fundamental number is 100 arms. The evolutionary tendency is type B with no supernumerary chromosomes; a first pair of big metacentric chromosomes is characteristic for Brycon, while no chromosomic sexual heteromorfism was detected.

La sabaleta Brycon henni, es un pez nativo del occidente colombiano importante para la seguridad alimentaria de las poblaciones ribereñas y para la pesca deportiva por sus característica combativas. El desarrollarse entre los 18 y 28ºC la convierte en una especie de cultivo promisoria. Un estudio citogenético a partir de células branquiales indicó diferentes complementos cromosómicos. Este trabajo aplicó la técnica de cultivo de linfocitos a muestras de sangre de adultos. Las muestras de sangre total fueron sembradas en 4 ml de medio de cultivo Ham-F12, suplementado con 0.5 ml de Suero Fetal Bovino y 0.7 ml del mitógeno Fitohemaglutinina M (Gibco®) durante 96 hr a 28ºC; 1.5 hr antes de la cosecha agregamos 100µl de Colcemid al 10% como factor antimitótico. Cada cultivo se incubó con 10 ml de solución hipotónica KCl 0.56% por 24 min a 37ºC, para continuar con tres fijaciones sucesivas, centrifugaciones y tinción Giemsa al 5%. Las mejores metafases fueron fotografiadas en microscopio, correspondientes a 6 machos y 8 hembras, indicando un número diploide de 50 cromosomas, clasificados en Metacéntricos (26M), Submetacéntricos (16SM) y Subtelocéntricos (8ST), para un número fundamental (NF) de 100 brazos. La tendencia evolutiva hallada fue de tipo B; no se encontraron cromosomas supernumerarios pero sí un primer par de cromosomas metacéntricos grandes, considerado marcador para el género Brycon, no determinante de heteromorfismo sexual. Estos resultados coinciden con los demás bricónidos investigados, en donde se podría considerar un ancestro común con un número cromosómico básico y cariotipos simétricos.Cytogenetic characterization of the neotropical fish Brycon henni (Pisces: Characidae). Brycon henni, is a native fish from Western Colombia is important as food and in sport fishing, and could be cultured in waters between 18 and 28ºC. A previous cytogenetic study in branchial cells indicated different chromosomal complements. Total blood samples were seeded in 4 ml Ham-F12 culture medium, supplemented with 0.5 ml Bovine Fetal Serum and 0.7 ml Phyitohemaglutinin M (Gibco®) during 96 hr at 28ºC; an antimitotic factor (100µl Colcemid® 10%) was added. Cells were incubated in 10 ml KCl hypotonic solution (0.56%) for 24 min at 37ºC, fixed in methanol; acetic acid (3: 1) three times, separated by centrifugations, extended drip, and the chromosomes slides were stained with 5% Giemsa (5%). The best metaphases (6 males and 8 females) were photographed. There was a diploid number of 50 chromosomes: Metacentrics (26M), Submetacentrics (16SM) and Subtelocentrics (8ST). The fundamental number is 100 arms. The evolutionary tendency is type B with no supernumerary chromosomes; a first pair of big metacentric chromosomes is characteristic for Brycon, while no chromosomic sexual heteromorfism was detected. Rev. Biol. Trop. 56 (4): 1619-1628. Epub 2008 December 12.

In acute myeloid leukemia (AML), FLT3 mutations are associated with a poor prognosis, particularly the internal tandem duplication (ITD/FLT3). In Latin America there are few epidemiological data about these mutations.This study assessed the prevalence of FLT3 mutations in patients with AML at four reference hematology centers from Latin America. We included 138 samples of patients attending the Hematology Service of three Mexican University Hospitals (Monterrey,México D.F. and Puebla) and one Colombian center (Medellín) with a diagnosis of AML from different morphologic subgroups according to the French-American-British classification from 2006 to 2011. AML was diagnosed by morphology according to the FAB classification, by immunohistochemical staining and/or by immunophenotype according to each particular case. For sample processing DNA was extracted from peripheral blood or bone marrow with the automatic Maxwell®16 System (Promega Corporation, Madison, WI) using the principle of cellular lyses and binding nucleic acids to magnetized silice particles or the QIAAmp DNA Blood Kit (QIAGEN, Mexico City). The quality and DNA concentration was evaluated with the NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies, Inc., Wilmington, DE). Then internal tandem duplication and kinase domain mutations detection was performed with the GeneAmp PCR System 9700 (Applied Biosystems, Foster City, CA), through amplification of exons 14,15 with specific primers of FLT3 gen region, using the Seeplex® FLT3 Genotyping kit (Seegene, Rockville, MD, USA) or according to Kottaridis et al (1). Later, an electrophoretic analysis of the amplified products was made in a 2% agarose gel stained with ethidium bromide or in polyacrylamide gel electrophoresis (PAGE) and were observed by transilumination. In the Puebla samples the products were analyzed by capillary electrophoresis (ABI3130, Applied Biosystems, Foster City, CA). For detection of D835X mutations the exon 20 amplicom was subjected to digestion with EcoRV and analyzed by 4.5% PAGE. The patients were cytogenetically classified into three risk groups: favorable, intermediate, and adverse. Results We analyzed 138 samples of AML patients and found FLT3 mutations in 28 patients, for a prevalence of 20.3%. The median age was 47 years (5-96). Only four patients had the KD FLT3 mutation (3% of total population). The FLT3 mutation positive group was older than the negative (47 vs. 39 years), had higher WBC/mm3 (66.0 vs. 56.4 x 109/dl), higher hemoglobin values (9.3 vs. 8.6 g/dl), and lower platelet counts (72.6 vs. 92.5 x109/dl), although there were not statistically significant differences. Thirteen patients had AML M2, nine the monocytic variety, four had M3 and two M1. On cytogenetics 25% , 62.5% and 12.5% had favorable, intermediate and unfavorable risk karyotypes respectively. The rate response to standard Induction Chemotherapy was 78.3 % for the FLT3 positive group vs. 74.1 % for the non-mutated group. Nineteen of 28 patients (67.8%) with FLT3 mutations died, compared to 47 of 100 (42.72%) in those without the mutation. The median survival was 4.9 months for the FLT3 mutated group vs 20.4 months for the FLT3 negative group, P= 0.009. The cytogenetic intermediate risk group (62.5%) was further analyzed and no statistically significant difference in overall survival between FLT3 non-mutated and FLT3 mutated patients was found (P= 0.22). Younger patients ( References 1. Kottaridis PD, Gale RE,Frew ME et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds importatnt prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood.2001; 98: 1752-1759 2. Emerenciano M, Meneses J, Vasquez ML et al, Brazilian Collaborative Study Groupof Infant Acute L. Clinical relevance of FLT3 gene abnormalities in Brazilian patients with infant leukemia.Leuk Lymphoma. 2008; 49 (12):2291-2297. Disclosures: No relevant conflicts of interest to declare.

Background Approximately 5% of all breast cancers can be attributed to a mutation in the BRCA1 or BRCA2 gene. The genetic component of breast cancer in Colombia has been, for the most part, studied on cases from the Bogota region. Five different founder mutations were in two studies of breast cancer patients in the Bogota region. It is important that the frequency of mutations be established among unselected cases of breast cancer of other regions of Colombia in order to estimate the genetic burden of this cancer in Colombia and to plan genetic services. The aim of this study was to establish the mutation frequencies of the BRCA genes in breast cancer patients unselected for family history or age, from Medellin, Colombia. Methods We enrolled 280 unselected women with breast cancer from a large public hospital in Medellin, Colombia. A detailed family history from each patient and a blood sample was obtained and processed for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques including a panel of recurrent Hispanic BRCA mutations which consists of fifty BRCA1 mutations and forty-six BRCA2 mutations, including the five recurrent Colombian BRCA mutations. All mutations were confirmed by direct sequencing. Results Genetic testing was successfully completed for 244 of the 280 cases (87%). Among the 244 cases, three deleterious mutations were identified (two in BRCA1 and one in BRCA2) representing 1.2% of the total. The average age of breast cancer in the mutation-positive cases was 34 years. The two BRCA1 mutations were known founder mutations (3450del4 in exon 11 and A1708E in exon 18). The BRCA2 mutation was in exon 11 (5844del5) and has not been previously reported in individuals of Colombian descent. Among the three mutation-positive families was a breast cancer family and two families with no history of breast or ovarian cancer. Conclusion The frequency of BRCA mutations in unselected breast cancer cases from the Medellin region of Colombia is low and is approximately 1.2%.