Extramedullary disease in acute promyelocytic leukemia: two-in-one disease

Abstract

In acute promyelocytic leukemia (APL), extramedullary disease (EMD) is particularly rare and shows special clinical and biological features. It is estimated that about 3-5% of APL patients will suffer extramedullary relapse. The most common site of EMD in APL is the central nervous system (CNS). At present, there are still many issues of EMD in APL needing further clarification, including pathogenesis, risk factors, prognosis and treatment. A better understanding of the biological mechanisms underlying EMD is important to be able to devise more effective CNS prophylaxis and induction-consolidation therapeutic strategies.

Figure 1

ATRA-driven differentiation of APL cells is associated with the upregulation of cellular adhesion molecules like LFA-1 and VLA-4. The mechanism of APL blasts adhesion to the endothelium may be further increased by interleukin-1, an effect which may be mediated via an increased expression of ICAM-1 and VCAM-1 on the CNS endothelium. Since both LFA-1 and VLA-4 are upregulated in APL blasts treated with retinoids, it is reasonable to suppose that the upregulation of these adhesion molecules might promote passage across the BBB of ATRA-treated APL cells, thereby creating the conditions for a subsequent CNS relapse. Moreover, CD56 expression on APL cells may also foster CNS relapse.