Leukaemic cells from chronic lymphocytic leukaemia patients undergo apoptosis following microtubule depolymerization and Lyn inhibition by nocodazole.
Br J Haematol
; 165(5): 659-72, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-24606526
ABSTRACT
Functional abnormalities of chronic lymphocytic leukaemia (CLL) cells may be related to the microtubular network of cell cytoskeleton; specifically tubulin involvement in cells after B-cell receptor engagement. As microtubule inhibitors could represent a therapeutic strategy for CLL, this study investigated the capability of nocodazole, a synthetic depolymerizing agent, to kill CLL leukaemic cells. We demonstrated that nocodazole was highly specific for the in vitro induction of apoptosis in leukaemic cells from 90 CLL patients, without affecting the viability of T-cells and/or mesenchymal stromal cells (MSCs) recovered from the same patients. Nocodazole was observed to overcome the pro-survival signals provided by MSCs. Competing with ATP for the nucleotide-binding site, nocodazole has been observed to turn off the high basal tyrosine phosphorylation of leukaemic cells mediated by the Src-kinase Lyn. Considering that most anti-microtubule drugs have limited clinical use because of their strong toxic effects, the high selectivity of nocodazole for leukaemic cells in CLL and its capability to bypass microenvironmental pro-survival stimuli, suggests the use of this inhibitor for designing new therapeutic strategies in CLL treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Linfocítica Crónica de Células B
/
Nocodazol
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Familia-src Quinasas
/
Moduladores de Tubulina
/
Microtúbulos
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Aged80
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Br J Haematol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Italia