Premium
Leukaemic cells from chronic lymphocytic leukaemia patients undergo apoptosis following microtubule depolymerization and L yn inhibition by nocodazole
Author(s) -
Frezzato Federica,
Trimarco Valentina,
Martini Veronica,
Gattazzo Cristina,
Ave Elisa,
Visentin Andrea,
Cabrelle Anna,
Olivieri Valeria,
Zambello Renato,
Facco Monica,
Zonta Francesca,
Cristiani Andrea,
Brunati Anna Maria,
Moro Stefano,
Semenzato Gianpietro,
Trentin Livio
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12815
Subject(s) - nocodazole , cancer research , chronic lymphocytic leukemia , apoptosis , microtubule , dasatinib , lyn , biology , stromal cell , tyrosine kinase , tubulin , leukemia , microbiology and biotechnology , cell , cytoskeleton , immunology , signal transduction , biochemistry
Summary 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 ( MSC s) recovered from the same patients. Nocodazole was observed to overcome the pro‐survival signals provided by MSC s. 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.