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PLC‐β2 monitors the drug‐induced release of differentiation blockade in tumoral myeloid precursors
Author(s) -
Brugnoli Federica,
Bovolenta Matteo,
Benedusi Mascia,
Miscia Sebastianó,
Capitani Silvano,
Bertagnolo Valeria
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20749
Subject(s) - promyelocyte , retinoic acid , acute promyelocytic leukemia , myeloid , cancer research , differentiation therapy , cellular differentiation , blockade , myeloid leukemia , pharmacology , tretinoin , microbiology and biotechnology , chemistry , immunology , biology , receptor , biochemistry , gene
The differentiation therapy in treatment of acute promyelocytic leukemia (APL), based on the administration of all‐trans retinoic acid (ATRA), is currently flanked with the use of As 2 O 3 , a safe and effective agent for patients showing a resistance to ATRA treatment. A synergy between ATRA and As 2 O 3 was also reported in inducing granulocytic differentiation of APL‐derived cells. We have demonstrated that phospholipase C‐β2 (PLC‐β2), highly expressed in neutrophils and nearly absent in tumoral promyelocytes, largely increases during ATRA treatment of APL‐derived cells and strongly correlates with the responsiveness of APL patients to ATRA‐based differentiating therapies. Here we report that, in APL‐derived cells, low doses of As 2 O 3 induce a slight increase of PLC‐β2 together with a moderate maturation, and cooperate with ATRA to provoke a significant increase of PLC‐β2 expression. Remarkably, the amounts of PLC‐β2 draw a parallel with the differentiation levels reached by both ATRA‐responsive and ‐resistant cells treated with ATRA/As 2 O 3 combinations. PLC‐β2 is not necessary for the progression of tumoral promyelocytes along the granulocytic lineage and is unable to overcome the differentiation block or to potentiate the agonist‐induced maturation. On the other hand, since its expression closely correlates with the differentiation level reached by APL‐derived cells induced to maturate by drugs presently employed in APL therapies, PLC‐β2 represents indeed a specific marker to test the ability of differentiation agents to induce the release of the maturation blockade of tumoral myeloid precursors. J. Cell. Biochem. 98: 160–173, 2006. © 2006 Wiley‐Liss, Inc.