Key Points Ten cases of an indolent T-cell lymphoproliferative disease of the gastrointestinal tract are reported. It is important to recognize this condition because it can be mistaken for aggressive T-cell lymphoma, which may lead to unnecessary therapy.

Mice deficient in the Flk-1 receptor tyrosine kinase are known to die in utero because of defective vascular and hematopoietic development. Here, we show that flk-1 ؊͞؊ embryonic stem cells are nevertheless able to differentiate into hematopoietic and endothelial cells in vitro, although they give rise to a greatly reduced number of blast colonies, a measure of hemangioblast potential. Furthermore, normal numbers of hematopoietic progenitors are found in 7.5-day postcoitum flk-1 ؊͞؊ embryos, even though 8.5-day postcoitum flk-1 ؊͞؊ embryos are known to be deficient in such cells. Our results suggest that hematopoietic͞endothelial progenitors arise independently of Flk-1, but that their subsequent migration and expansion require a Flk-1-mediated signal.The vascular endothelial growth factor (VEGF) receptor Flk-1 is known to play a key role in the regulation of embryonic vascular and hematopoietic development. In the mouse embryo, flk-1 expression can be detected in presumptive mesodermal yolk-sac blood-island progenitors as early as 7.0 days postcoitum (dpc) (1, 2). As has been described recently (3), mice deficient in Flk-1 do not develop blood vessels or yolk sac blood islands and die between 8.5 and 9.5 dpc. In chimeric aggregation studies with wild-type embryos, flk-1 Ϫ͞Ϫ embryonic stem (ES) cells fail to participate in vessel formation or to contribute to primitive or definitive hematopoiesis in vivo, suggesting that Flk-1 inactivation results in a cell autonomous endothelial and hematopoietic defect (4). Taken together, these studies suggest that Flk-1 may mark the common endothelial͞hematopoietic precursor, the hemangioblast. The recently identified blast colony-forming cell (BL-CFC), an in vitro ES cell derivative, has confirmed the existence of such a cell. In response to VEGF, BL-CFCs form blast colonies containing Flk-1-expressing blast cells that give rise to primitive, definitive hematopoietic and endothelial cells in vitro (5, 6). Taken together, these findings strongly suggest that the VEGF͞ Flk-1 interaction is important for hemangioblast development.Although all of these studies suggest that the Flk-1 receptor is important in embryonic endothelial and hematopoietic development, the precise nature of its role remains undefined. In particular, the contribution of Flk-1 to hemangioblast formation is unclear, as flk-1 Ϫ͞Ϫ and VEGF ϩ͞Ϫ mice show residual hematopoietic and endothelial activity (3,7,8) and Flk-1-deficient ES cells appear to retain a degree of hematopoietic potential in vitro (4). To define the developmental role of Flk-1 more systematically, we have characterized the hematopoietic and endothelial potential of flk-1 Ϫ͞Ϫ ES cells and embryos in greater detail. And in particular, as the BL-CFC assay should allow the developmental consequences of Flk-1 deficiency during the very early VEGF-dependent stage of hematopoiesis to be analyzed quantitatively (5), we have assessed the ability of flk-1 Ϫ͞Ϫ ES cells to give rise to blast colonies. We report that Flk-1-deficient BL-CFCs appear...