3 years ago

Leptin-deficient obesity prolongs survival in a murine model of myelodysplastic syndrome.

Jaye Chin-Dusting, David J Curtis, Michael J Kraakman, Dragana Dragoljevic, Man K S Lee, Andrew A Guirguis, Christian J Stolz, Annas Al-Sharea, Michelle C Flynn, Helene L Kammoun, Andrew J Murphy, Graeme I Lancaster
Obesity enhances the risk of developing myelodysplastic syndromes. However, the effect of obesity on survival is unclear. Obese people present with monocytosis due to inflammatory signals emanating from obese adipose tissue. We hypothesized that obesity-induced myelopoiesis would promote the transition of myelodysplastic syndrome to acute myeloid leukemia and accelerate mortality in obesity. Obese Ob/Ob mice or their lean littermate controls received a bone marrow transplant from NUP98-HOXD13 transgenic mice, a model of myelodysplastic syndrome. The metabolic parameters of the mice were examined throughout the course of the study, as were blood leukocytes. Myeloid cells were analyzed in the bone, spleen, liver and adipose tissue by flow cytometry halfway through the disease progression and at the endpoint. Survival curves were also calculated. Contrary to our hypothesis, transplantation of NUP98-HOXD13 bone marrow into obese recipient mice significantly increased survival time compared with lean recipient controls. While monocyte skewing was exacerbated in obese mice receiving NUP98-HOXD13 bone marrow, transformation to acute myeloid leukemia was not enhanced. Increased survival of obese mice was associated with a preservation of fat mass as well as increased myeloid cell deposition within the adipose tissue and a concomitant reduction in detrimental myeloid cell accumulation within other organs. This study revealed that obesity increases survival in animals with myelodysplastic syndrome. This may be due to the greater fat mass of Ob/Ob mice, which acts as a sink for myeloid cells, preventing their accumulation in other key organs such as the liver.

Publisher URL: http://doi.org/10.3324/haematol.2017.181958

DOI: 10.3324/haematol.2017.181958

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