Adhesion Deregulation in Acute Myeloid Leukaemia

Abstract

Cell adhesion is a process through which cells interact with and attach to neighboring cells or matrix using specialized surface cell adhesion molecules (AMs). Adhesion plays an important role in normal haematopoiesis and in acute myeloid leukaemia (AML). AML blasts express many of the AMs identified on normal haematopoietic precursors. Differential expression of AMs between normal haematopoietic cells and leukaemic blasts has been documented to a variable extent, likely reflecting the heterogeneity of the disease. AMs govern a variety of processes within the bone marrow (BM), such as migration, homing, and quiescence. AML blasts home to the BM, as the AM-mediated interaction with the niche protects them from chemotherapeutic agents. On the contrary, they detach from the niches and move from the BM into the peripheral blood to colonize other sites, i.e., the spleen and liver, possibly in a process that is reminiscent of epithelial-to-mesenchymal-transition in metastatic solid cancers. The expression of AMs has a prognostic impact and there are ongoing efforts to therapeutically target adhesion in the fight against leukaemia.

Keywords: EMT; acute myeloid leukaemia; adhesion molecules.

Figure 1

Expression pattern of AMs, chemokine receptors and other adhesion-modulating proteins on the surface of HSC and LSC. The molecules in common are depicted on the blue-red cell (left to lower right), while the molecules expressed exclusively on LSC are drawn on the surface of the red cell (upper right).

Figure 2

The balance between homing and migration in normal and leukaemic cells. (A) Normal HSCs home to the bone marrow niches and exit the niches in response to differentiating and mobilizing stimuli. (B) LSCs use the niche for protection from chemotherapeutic agents and detach from it in order to spread possibly deploying the EMT machinery.

Figure 3

Therapeutically targetable AMs and interactions between AMs and their ligands on the surface of LSCs. The question mark denotes inhibitors of AMs targeted in other malignancies or in vitro.