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Doctoral Thesis
DOI
10.11606/T.42.2009.tde-07102009-155229
Document
Author
Full name
Monica Alexandra Yon Castro
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Mendes, Joao Gustavo Pessini Amarante (President)
Barbuto, Jose Alexandre Marzagao
Chammas, Roger
Chauffaille, Maria de Lourdes Lopes Ferrari
Rizzo, Luiz Vicente
Title in Portuguese
Expressão de galectina-1 e -3 na leucemia mielóide crônica e sua contribuição para a progressão da doença.
Keywords in Portuguese
BCR-ABL
Galectina-1
Galectina-3
Imunologia
Leucemia mielóide crônica
Tirosina quinase
Tumorigênese
Abstract in Portuguese
A galectina-1 (LGALS1) participa em diferentes etapas da neoplasia, mas sua função na leucemia mielóide crônica (LMC) é desconhecida. Neste trabalho, a expressão etópica de BCR-ABL selvagem, mas não de BCR-ABL quinase deficiente, em linhagens celulares hematopoéticas, resultou em aumento de LGALS1. O efeito foi revertido com a inibição da tirosina quinase pelo mesilato de imatinibe. Este resultado indicou que a galectina-1 é modulada pela atividade tirosina-quinase de BCR-ABL. Em pacientes com LMC, a maior expressão de LGALS1 foi correlacionada a altos níveis de BCR-ABL, progressão da doença e a um tempo de sobrevida menor. Adicionalmente, as células K562 com LGALS1 inibida por RNA de interferência exibiram crescimento mais lento do que as células K562 com LGALS1 intacta, em camundongos nude. Portanto, o pior prognóstico de pacientes com altos níveis de galectina-1 sugere um efeito cooperativo de galectina-1 na tumorigênese de BCR-ABL reforçando o conceito de que a galectina-1 é um forte candidato para intervenção terapêutica na LMC.
Title in English
Expression of galectin-1 and -3 in chronic myeloid leukemia and its contribution to disease progression.
Keywords in English
BCR-ABL
Chronic myeloid leukemia
Galectin-1
Galectin-3
Immunology
Tumorigenesis
Tyrosine kinase
Abstract in English
Galectin-1 (LGALS1) participates in different steps of neoplasia but its role in chronic myeloid leukemia (CML) is unknown. In this work, ectopic expression of wild-type but not kinase-deficient BCR-ABL in different hematopoietic cells resulted in LGALS1 upregulation. Tyrosine-kinase inhibition by imatinib mesylate reversed this effect. This result indicate that galectin-1 is modulated by tyrosine kinase activity. In CML patients, the elevated expression of LGALS1 was correlated with high BCR-ABL levels, disease progression and shorter survival time. Additionally, in nude mice, LGALS1-deficient K562 cells obtained by RNA interference were less efficient in tumor formation than control K562 cells. Therefore, the worst prognosis in patients bearing high LGALS1 levels suggests a cooperative role for galectin-1 in BCR-ABL-positive leukemia and support the concept that galectin-1 is a strong candidate for CML therapeutic intervention.
 
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Publishing Date
2009-12-04
 
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