<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0123-9015</journal-id>
<journal-title><![CDATA[Revista Colombiana de Cancerología]]></journal-title>
<abbrev-journal-title><![CDATA[rev.colomb.cancerol.]]></abbrev-journal-title>
<issn>0123-9015</issn>
<publisher>
<publisher-name><![CDATA[Instituto Nacional de Cancerología E.S.E.]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0123-90152018000100008</article-id>
<article-id pub-id-type="doi">10.1016/j.rccan.2018.02.001</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Detección de mutaciones en el dominio tirosina quinasa de BCR-ABL1 en pacientes colombianos con leucemia mieloide crónica LMC, resistentes al imatinib]]></article-title>
<article-title xml:lang="en"><![CDATA[Detection of BCR-ABL1 tyrosine kinase domain mutations in chronic myeloid leukaemia patients with Imatinib resistance in Colombia]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vásquez Palacio]]></surname>
<given-names><![CDATA[Gonzalo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ramírez]]></surname>
<given-names><![CDATA[Gloria Cecilia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Muskus]]></surname>
<given-names><![CDATA[Carlos Enrique]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Domingo Torres]]></surname>
<given-names><![CDATA[José]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Aya]]></surname>
<given-names><![CDATA[Carlos Alberto]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad de Antioquia Facultad de Medicina Unidad de Genética Médica, Departamento de Pediatría]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad de Antioquia Facultad de Medicina Programa de Estudio y Control de Enfermedades Tropicales, PECET]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad de Antioquia Facultad de Medicina Departamento de Medicina Interna]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>03</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>03</month>
<year>2018</year>
</pub-date>
<volume>22</volume>
<numero>1</numero>
<fpage>8</fpage>
<lpage>17</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0123-90152018000100008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0123-90152018000100008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0123-90152018000100008&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[ Resumen  Introducción:  Las mutaciones en el dominio BCR-ABL1, tirosina quinasa (TK) son mecanismos importantes de resistencia de los inhibidores de la tirosina quinasa (ITK) en pacientes con leucemia mieloide crónica (LMC).  Objetivo:  Determinar el tipo y la frecuencia de las mutaciones en el dominio tirosina quinasa del gen BCR-ABL1, asociadas con falla en la respuesta al tratamiento con imatinib en pacientes con LMC y correlacionar el perfil de mutaciones con los hallazgos clínicos, demográficos, respuesta citogenética y respuesta molecular.  Materiales y métodos:  Se realizó un estudio descriptivo de tipo prospectivo en pacientes con LMC en tratamiento con IMATINIB a quienes se les realizó cariotipo y análisis de mutaciones del dominio BCR-ABL1 mediante la técnica de PCR anidada.  Resultados:  De los 23 pacientes estudiados en cuatro se encontraron mutaciones: dos presentaron la mutación E255K, uno presentó la mutación H396P y otro presentó doble mutación L387L y T389P. Las mutaciones E255K que se ubican en la región P-loop y H396P en A-loop se asocian con mal pronóstico. La mutación T389P localizada en la región A-loop no está informada en algunas bases de datos.  Conclusiones:  En este estudio encontramos cuatro mutaciones en el dominio tirosina quinasa (E255K, H396P, L387L y T389P) que podrían aportar información valiosa y guiar las decisiones de tratamiento. Es importante destacar que esta investigación de análisis mutacional del dominio BCR-ABL es la primera que se realiza en el país con la particularidad adicional de cubrir una población triétnica.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract 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.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Leucemia mieloide crónica]]></kwd>
<kwd lng="es"><![CDATA[Inhibidor de tirosina quinasa]]></kwd>
<kwd lng="es"><![CDATA[Mutaciones en el dominio tirosina quinasa]]></kwd>
<kwd lng="es"><![CDATA[Resistencia a imatinib]]></kwd>
<kwd lng="es"><![CDATA[BCR-ABL1]]></kwd>
<kwd lng="en"><![CDATA[Chronic Myeloid Leukaemia]]></kwd>
<kwd lng="en"><![CDATA[Tyrosine Kinase Inhibitors]]></kwd>
<kwd lng="en"><![CDATA[KD mutations]]></kwd>
<kwd lng="en"><![CDATA[Resistance]]></kwd>
<kwd lng="en"><![CDATA[Imatinib resistance]]></kwd>
<kwd lng="en"><![CDATA[BCR-ABL1]]></kwd>
</kwd-group>
</article-meta>
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