Cytoskeletal regulatory gene expression and migratory properties of B-cell progenitors are affected by the ETV6-RUNX1 rearrangement

Chiara Palmi, Grazia Fazio, Angela M. Savino, Julia Procter, Louise Howell, Valeria Cazzaniga, Margherita Vieri, Giulia Longinotti, Ilaria Brunati, Valentina Andrè, Pamela Della Mina, Antonello Villa, Mel Greaves, Andrea Biondi*, Giovanna D'Amico, Anthony Ford, Giovanni Cazzaniga

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Although the ETV6-RUNX1 fusion is a frequent initiating event in childhood leukemia, its role in leukemogenesis is only partly understood. The main impact of the fusion itself is to generate and sustain a clone of clinically silent preleukemic B-cell progenitors (BCP). Additional oncogenic hits, occurring even several years later, are required for overt disease. The understanding of the features and interactions of ETV6-RUNX1-positive cells during this "latency" period may explain how these silent cells can persist and whether they could be prone to additional genetic changes. In this study, two in vitro murine models were used to investigate whether ETV6-RUNX1 alters the cellular adhesion and migration properties of BCP. ETV6-RUNX1-expressing cells showed a significant defect in the chemotactic response to CXCL12, caused by a block in CXCR4 signaling, as demonstrated by inhibition of CXCL12-associated calcium flux and lack of ERK phosphorylation. Moreover, the induction of ETV6-RUNX1 caused changes in the expression of cell-surface adhesion molecules. The expression of genes regulating the cytoskeleton was also affected, resulting in a block of CDC42 signaling. The abnormalities described here could alter the interaction of ETV6-RUNX1 preleukemic BCP with the microenvironment and contribute to the pathogenesis of the disease.

Original languageEnglish
Pages (from-to)1796-1806
Number of pages11
JournalMolecular Cancer Research
Issue number12
StatePublished - 1 Dec 2014
Externally publishedYes


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