Histopathological characterization of the MPD induced by JAK2 V617F.

<div><p>(A–C): Hematoxylin and eosin stains (magnification 500×) of BM (A), spleen (B), and liver (C) from representative polycythemic recipients of JAK2 V617F-transduced BM.</p> <p>In the spleen, a lymphoid follicle (f) and an area of erythroid hyperplasia (e) are indicated.</p> <p>The same tissues from recipients of JAK2 WT-transduced BM showed no pathological changes compared with normal controls (data not shown).</p> <p>(D) Wright-Giemsa stains (top panels) and acetylcholinesterase stains (bottom panels) of purified megakaryocytes from recipients of JAK2 V617F-transduced BM (right panels) or normal control mice (left panels).</p> <p>Note the preponderance of small megakaryocytes from JAK2 V617F recipients, some of which are undergoing proplatelet formation (arrowheads), accompanied by abnormal mitoses with low apparent ploidy (insert).</p> <p>(E) Flow cytometric analysis of BM and spleen from a representative recipient of JAK2 V617F-transduced BM, stained with the indicated hematopoietic lineage antigens.</p> <p>The mean fluorescence intensity of GFP expressed from JAK2 retroviral provirus was reproducibly and significantly lower than the GFP fluorescence of a comparable BCR-ABL retrovirus (data not shown).</p> <p>Note the shift of GFP^+/lo erythropoiesis (TER-119⁺) from BM to spleen and the expression of GFP in low abundance CD41⁺ megakaryocytes.</p> <p>(F) Flow cytometric assessment of erythrocyte differentiation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000018#pone.0000018-Socolovsky1" target="_blank">[47]</a>, assessed by expression of transferrin receptor (CD71) and TER-119 in splenocytes of recipients of JAK2 WT-transduced (top) and JAK2 V617F-transduced (bottom) BM.</p> <p>Note the increased (3.5-fold) population of CD71^+/loTER-119⁺ erythroblasts in JAK2 V617F recipients.</p>