Signal Transduction Pathways Underlying the Expression of Tissue Factor and Thrombomodulin in Promyelocytic Cells Induced to Differentiate by Retinoid Acid and Dibutyryl cAMP

Chari López-Pedrera; Pablo M. Dobado-Berrios; Rosa Ros; Antonio Torres; Socorro García-Navarro; Mercé Jardí; Jordi Félez; Francisco Velasco

doi:10.1055/s-0037-1615959

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(06): 1031-1036
DOI: 10.1055/s-0037-1615959

Review Article

Schattauer GmbH

Signal Transduction Pathways Underlying the Expression of Tissue Factor and Thrombomodulin in Promyelocytic Cells Induced to Differentiate by Retinoid Acid and Dibutyryl cAMP

Chari López-Pedrera

¹Departments of Research, Reina Sofia University Hospital, Cordoba

,

Pablo M. Dobado-Berrios

¹Departments of Research, Reina Sofia University Hospital, Cordoba

,

Rosa Ros

¹Departments of Research, Reina Sofia University Hospital, Cordoba

,

Antonio Torres

²Haematology and Haemotherapy, Reina Sofia University Hospital, Cordoba

,

Socorro García-Navarro

³Cell Biology, University of Cordoba, Cordoba

,

Mercé Jardí

⁴Institut de Recerca Oncològica, Hospital Duran i Reynals, Barcelona, Spain

,

Jordi Félez

⁴Institut de Recerca Oncològica, Hospital Duran i Reynals, Barcelona, Spain

,

Francisco Velasco

²Haematology and Haemotherapy, Reina Sofia University Hospital, Cordoba

› Author Affiliations

Abstract

Summary

Acute promyelocytic leukaemia (APL) may be associated with disseminated intravascular coagulation, as a result of increased tissue factor (TF) expression and reduced thrombomodulin (TM) expression by APL blast cells. During retinoid acid (RA)- and dibutyryl cAMP (dbcAMP)-induced differentiation of the APL cells, there is a marked up-modulation of both the protein kinase A (PKA) and C (PKC) activities. In order to further assess whether these kinases are intimately associated with both the differentiation process and the regulation of TF and TM expression, we have correlated the modulation of their respective pathways with the extent of differentiation and modulation of these cellular receptors. NB4 cells were incubated with all-trans-RA (ATRA) or dbcAMP for up to 48 h. The contribution of phospholipase C (PLC), inositol phosphate (IP), PKC and PKA in the expression of CD11b, TF and TM was studied by the use of specific inhibitors. Myo-inositol uptake and PKC activity increased in cells induced to differentiate by ATRA but the retinoid did not affect cAMP levels or PKA activity. Under treatment with dbcAMP, PKA activity was increased while inositol uptake and PKC activity remained unchanged. Our results show that the effects of ATRA and dbcAMP on promyelocytic cells are closely related, respectively, to the PLC/IP/PKC and the cAMP/PKA pathways. In cells induced to differentiate by ATRA, CD11b expression seems more closely related to inositol uptake than to PKC activity while the expression of TF and TM show the opposite pattern, which suggests cellular events regulated at a different level within a common signal transduction pathway.

Key words

Cell differentiation - promyelocytic cells - signal transduction - tissue factor - thrombomodulin

Full Text

References

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