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Obesity and myelodysplasia
performed alongside healthy lean and obese controls for comparative analysis. Consistent with the data obtained throughout the course of the disease, monocytosis was observed in lean MDS mice, and this effect was exacerbat- ed in the obese MDS mice (Figure 3A). The inefficient hematopoiesis which is characteristic of MDS occurred at similar levels in lean and obese MDS mice, both of which presented with severe lymphopenia, reduced circulating progenitor cells, and anemia (Figure 3B-F). Anemia was
accompanied by macrocytosis, as demonstrated by the significantly increased mean corpuscular volume, indica- tive of RBC volume (Figure 3G). Platelet counts were also reduced with MDS, irrespective of obesity status (Figure 3H). Finally, prominent splenomegaly occurred in MDS mice, consistent with the monocytosis and aberrant extramedullary myelopoiesis observed at the seven- month time point (Figure 3I,J; Figure 1E,H). Consistent with MDS progression, and irrespective of body weight,
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Figure 3. Ob/Ob mice exhibit a similar disease phenotype at MDS/AML endpoint despite aggravated monocytosis. Ob/Ob mice and WT littermate controls trans- planted with either WT or NHD13 bone marrow (BM) were followed until the development of MDS symptoms required euthanasia. Blood flow cytometry analysis of (A) myeloid cells, (B) lymphocytes and (C) progenitor cells. CBC analysis of (D) red blood cells, (E) hemoglobin, (F) hematocrit, (G) mean corpuscular volume and (H) platelets. (I) Spleen weights and representative images, scale 0.5cm. (J) Flow cytometry analysis of HSPCs and myeloid progenitors in the BM. (K) Representative images of BM from lean and Ob/Ob mice, arrows indicate dilated blood vessels, A indicates adipocytes. (L) Flow cytometry analysis of HSPCs in the spleen. (A-I); n=11-16; (J-L); n=4-8. All data expressed as mean ± SEM. *P<0.05, for obesity effect; #P<0.05, for MDS effect as analyzed by 2-way ANOVA. WT: wild-type; RBC: red blood cell; HSPC: hematopoietic stem and progenitor cell; CMP: common myeloid progenitor; GMP: granulocyte-macrophage progenitor; MEP: megakaryocyte-ery- throid progenitor; MCV: mean corpuscular volume.
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