Bone marrow malignancies as paradigms of dysfunctional cell adhesion mechanisms

In adult bone marrow (BM), hematopoietic stem/progenitor cells (HSPCs) reside in micro-environments which provide instructions for self-renewal, survival, proliferation, differentiation and migration. Adequate response to such complex signals implies communication between HSCs, BM stroma and extracellular matrix molecules (ECM). This is achieved mainly through adhesion molecules. Malignant hematopoietic cells also interact with the BM microenvironment, which provides them with proliferative and survival advantages. Most of the studies on haematological diseases describe cell-ECM interactions as key mechanisms in tumor progression, while genetic alterations of HSC are considered major initiators of the malignant process. However, accumulating evidence suggests that an altered BM microenvironment provides anomalous cell adhesion signals, facilitating tumor initiation. Myeloproliferative and myelodysplastic syndromes are good examples of hematological disorders where alterations in BM microenvironment may play an important role in disease initiation. This review discusses the role for adhesion signals in regulating the BM microenvironment in normalcy and disease.