Bmi-1 expression is increased in dogs suffering from immune-mediated haemolytic anaemia

Abstract

Background – Immune-mediated haemolytic anaemia (IMHA) is one of the most common types of anaemia in dogs. In haematopoiesis, the protein BMI-1 determines postnatal self-renewal of haematopoietic stem cells (HSC).

Objectives – To provide new insights in haematopoiesis for dogs suffering from IMHA by investigating gene expression of Bmi-1.

Methods – Blood samples from 28 anaemic canine patients referred to the Department of Clinical Sciences of Companion Animals Utrecht University were analysed for Bmi-1 expression levels, including upstream and downstream targets using quantitative PCR.

Results – Bmi-1 expression shows 3-fold elevated levels in patients suffering from IMHA compared to healthy individuals. Upstream factors Zeb1 and E2f1 showed significant increase in mRNA levels in all anaemia cases, where Zeb1 was upregulated in IMHA cases. Surprisingly, cell cycle inhibitors p19Arf and p27, often inhibited by BMI-1, showed 1.5-fold and 4.1-fold increase in comparison to control cases, respectively.

Conclusions – Bmi-1 and p27 showed contrasting results regarding patients suffering from IMHA. Further research should be directed at locating p27 expression to either bone marrow or whole blood to clarify the event of apoptosis or haemolysis. This may elucidate the lack of a regenerative response in a lot of cases of IMHA. Interaction between BMI-1 and p27 and possible disturbance of this interaction in IMHA should also be examined. In this way, a role for dysfunctional haematopoiesis in pathophysiology of non-regenerative IMHA can be explored.