Obesity is a risk factor for several cancers and is also associated with the blood disorder, myelodysplastic syndrome (MDS). MDS can evolve to acute myeloid leukemia (AML), accounting for 30% of deaths in MDS patients. We recently showed that obesity is associated with increased haematopoiesis and particularly myelopoiesis in rodent models and we hypothesized this could promote the development of MDS to AML and reduce survival.
We used genetically obese ob/ob mice and their wild-type littermates transplanted with bone marrow from wild-type or NUP98-HOXD13(NHD13) transgenic mice. Body composition was assessed over time and blood sampled monthly for immune cell profiling for signs of MDS or AML. When terminally ill, mice were euthanized and organs examined for immune cell infiltrate. In parallel, diet-induced-obese (DIO) C57Bl6 mice and their lean counterparts were subjected to the aggressive MLL-ENL AML pathology and analysed in a similar way.
Surprisingly, NHD13-recipients ob/ob mice exhibited a significantly prolonged survival when compared to lean counterparts carrying NHD13 (median survival 308 days vs 209 days in lean mice, p<0.01). Monocytosis was aggravated in NHD13 ob/ob, however analyses showed increased recruitment of immune cells in the adipose tissue of NHD13 ob/ob mice while less leukemic cells were found in the liver and spleen. No survival advantage was observed in the DIO mice despite increased immune cells localizing to the adipose tissue.
This enhanced survival observed in ob/ob mice subjected to MDS appears to be associated with the homing of leukemic cells into the adipose tissue, potentially protecting mice from cachexia and liver and spleen failure. This enhanced survival was not reproduced in DIO mice exposed to an aggressive AML model.