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Key Points• Conditional Gata2-deficient mice have profoundly reduced DC populations.• Gata2 deficiency in DC progenitors reduced the expression of myeloid-related genes and increased that of T-lymphocyte-related genes.Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 1190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation. (Blood. 2016;128(4):508-518)

Background: S-adenosylmethionine-dependent methyltransferase inhibitor, DZNep, targets the degradation of histone methyltransferase EZH2 that catalyzes H3K27 trimethylation.Results: DZNep induced erythroid-related genes, which may not be directly related to EZH2 inhibition but may be partly associated with reduced protein level of hematopoietic corepressor ETO2.Conclusion: DZNep has the capacity to induce erythroid differentiation.Significance: Our data may be exploited for therapeutic applications for hematological diseases, including anemia.

Summary There is little information regarding the lymphangiogenesis of malignant lymphoma. In this study, we evaluated the lymphangiogenesis and angiogenesis in 44 lymph nodes of 39 malignant lymphomas and five non‐reactive normal lymph nodes, based on the lymphatic vessel density (LVD) and microvessel density (MVD) calculated by the computer‐assisted assessment of vessel density. The LVD of malignant lymphomas was significantly higher than that of non‐reactive normal lymph nodes, irrespective of subtypes (P = 0·00077). On the contrary, there was no difference in MVD between malignant lymphomas and non‐reactive normal lymph nodes, except for diffuse large B cell lymphomas, which had a significantly low value of MVD, in comparison with non‐reactive normal lymph nodes (P = 0·009). We further examined the expression of vascular endothelial growth factor (VEGF)‐C and VEGF‐A, which function on lymphangiogenesis in lymph node samples. VEGF‐C was expressed in 36 of 39 malignant lymphomas. All 39 of the malignant lymphoma samples expressed VEGF‐A. Furthermore, the level of LVD and VEGF‐A or VEGF‐C was positively correlated. These findings suggest that lymphangiogenesis is actively developed in lymph nodes of malignant lymphomas and it may be induced by both VEGF‐A and VEGF‐C secreted from lymphoma cells.