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M.J. Kraakman et al.
mice that were deemed to have died from cytopenias could have potentially developed aplastic anemia, as the morphology of the bone marrow and numbers of circulat- ing cells is similar to that described in this disease.
This study has a number of limitations which should be taken into account when interpreting our findings. Firstly, we used a genetic model of obesity, where leptin is defi- cient, thus causing hyperphagia. While this model is key in maintaining adiposity, it does not reflect a scenario where a change in diet drives obesity, in which, for example, changes in lipids may influence the transformation of the disease. Additionally, a role for leptin in the evolution of MDS cannot be excluded. Further, we opted to perform BMTs, as opposed to crossing the NHD13 mice with the Ob/Ob mice. Whether the hematopoietic stress associated with transplantation and engraftment altered the course of the disease is probably unlikely, but should be kept in mind. Finally, we only tested one model of MDS; whether this holds true in other models is yet to be determined.
In the study herein, we have demonstrated that obesity confers a survival advantage when mice are confronted with NHD13-induced MDS. It appears that the increased adiposity allows for dampening of the systemic leukemic
insult, as leukemic cells preferentially home to the adipose tissue, protecting vital organs such as the liver and spleen. Additionally, maintaining adequate fat stores per se may also contribute to the improved survival observed in obese MDS mice. Our findings support the growing literature suggesting that despite increased incidences of MDS and AML in obese patients, their overall survival may not be different to lean patients and, in some instances, may even be prolonged. Thus, taken together with the recent find- ings of Carey et al.,17 it may also be important to under- stand the cytokine profile of the patients before treatment, to ensure more effective eradication of the leukemia and to promote the restoration of normal hematopoiesis (i.e., inhibiting IL-1β in obese patients).
Funding
This work was supported by NHMRC grants (APP1083138, APP1106154 and APP1142938) to AJM. MJK is a Russell Berrie Foundation Scholar in Diabetes Research from the Naomi Berrie Diabetes Centre. AJM is supported by a Career Development Fellowship from the NHMRC (APP1085752), a Future Leader Fellowship from the National Heart Foundation (100440) and a Centenary Award from CSL.
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