The Effects of the Retinoid Drug Acitretin on CLL Cells with Emphasis on CD38 Expression and Cell Homing

Chronic lymphocytic leukaemia is a B- cell malignancy that has been the subject of a great deal of progress both in understanding disease pathophysiology and in the development of new therapies. The recognition of a subgroup of patients that responds poorly to standard therapy has inspired a plethora of research into improving treatment outcomes.

Retinoids have well-reported effects as anti-proliferation agents and have an established role in promoting cell differentiation. These properties have led them to be extensively studied in cancers in the contexts of prophylaxis and treatment.

In this study we explore the effects of the retinoid derivative acitretin on CLL cell viability, migration and CD38 expression in vitro.

In our clinical practice, a patient with stage A CLL as well as a diagnosis of squamouscell carcinoma of the skin was started on acitretin for the purpose of controlling his skin cancer. During follow-up it was noted that his lymphocyte count normalised within a month of starting acitretin. This observation led to preliminary in vitro studies investigating acitretin on primary patient cells.

Acitretin significantly increased CD38 expression in MEC-1 cells as well as in CLL cells from CD38-positive patient samples but did so to a far lesser degree on samples from CD38-negative patients. We also show that acitretin reduced the migration of CLL cells toward CXCL12 in the majority of samples tested. Acitretin however had a very modest effect on CLL viability and apoptosis.

Our results provide evidence that retinoids may have a role to play as an adjunct to drug treatment in CLL. We suggest that they should be considered for further studies in vivo and in perhaps in clinical trials, and that particular consideration should be given to studying them in combination with anti-CD38 monoclonal antibody drugs.