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Abnormal growth factor modulation of β1‐integrin‐mediated adhesion in chronic myelogenous leukaemia haematopoietic progenitors
Author(s) -
Bhatia Ravi,
Munthe Heidi A.,
Forman Stephen J.
Publication year - 2001
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 - 10.1046/j.1365-2141.2001.03192.x
Subject(s) - progenitor cell , chronic myelogenous leukemia , haematopoiesis , integrin , microbiology and biotechnology , stem cell , biology , cancer research , integrin linked kinase , adhesion , cell adhesion , immunology , chemistry , leukemia , cell , kinase , protein kinase a , genetics , organic chemistry , cyclin dependent kinase 2
Abnormal progenitor circulation and extramedullary haematopoiesis are characteristic features of chronic myelogenous leukaemia (CML). Growth factor (GF) and β1‐integrin interactions play an important role in regulation of progenitor trafficking to and from the marrow space. CML progenitors demonstrate abnormal β1‐integrin‐mediated adhesion to fibronectin (FN). In the present study we investigated whether GF modulation of β1‐integrin‐mediated adhesion and migration was altered in CML progenitors. Culture with low concentrations of GF enhanced normal progenitor adhesion to FN compared with no GF, but failed to enhance CML progenitor adhesion to FN. Similarly, high concentrations of selected GF rapidly enhanced β1‐integrin‐mediated adhesion of normal progenitors to FN through a phosphotidylinositol‐3 (PI‐3) kinase‐dependent mechanism, but failed to increase CML progenitor adhesion. Exposure to a BCR–ABL tyrosine kinase inhibitor restored GF modulation of CML progenitor adhesion. CML colony‐forming cells (CFC) demonstrated increased migration across FN‐coated transwells compared with normal CFC in the absence of GF. The addition of stem cell factor resulted in enhanced migration of CML and normal CFC on FN. In conclusion, GF stimulation failed to enhance integrin‐mediated adhesion but enhanced migration in CML progenitors on FN. BCR–ABL induced abnormalities in GF–integrin interactions could contribute to abnormal circulation and microenvironmental localization of CML progenitors.