Ying Guo

Key Points Transgenic expression of ASXL1aa1-587 truncating protein in the hematopoietic system leads to diverse myeloid malignancies in mice. ASXL1aa1-587 gains an interaction with BRD4 and Asxl1Y588XTg hematopoietic stem/progenitor cells are hypersensitive to BET bromodomain inhibitors.

Rapid evolutionary radiations are among the most challenging phylogenetic problems, wherein different types of data (e.g., morphology and molecular) or genetic markers (e.g., nuclear and organelle) often yield inconsistent results. The tribe Arundinarieae, that is, the temperate bamboos, is a clade of tetraploid originated 22 Ma and subsequently radiated in East Asia. Previous studies of Arundinarieae have found conflicting relationships and/or low support. Here, we obtain nuclear markers from ddRAD data for 213 Arundinarieae taxa and parallel sampling of chloroplast genomes from genome skimming for 147 taxa. We first assess the feasibility of using ddRAD-seq data for phylogenetic estimates of paleopolyploid and rapidly radiated lineages, optimize clustering thresholds, and analysis workflow for orthology identification. Reference-based ddRAD data assembly approaches perform well and yield strongly supported relationships that are generally concordant with morphology-based taxonomy. We recover five major lineages, two of which are notable (the pachymorph and leptomorph lineages), in that they correspond with distinct rhizome morphologies. By contrast, the phylogeny from chloroplast genomes differed significantly. Based on multiple lines of evidence, the ddRAD tree is favored as the best species tree estimation for temperate bamboos. Using a time-calibrated ddRAD tree, we find that Arundinarieae diversified rapidly around the mid-Miocene corresponding with intensification of the East Asian monsoon and the evolution of key innovations including the leptomorph rhizomes. Our results provide a highly resolved phylogeny of Arundinarieae, shed new light on the radiation and reticulate evolutionary history of this tribe, and provide an empirical example for the study of recalcitrant plant radiations. [Arundinarieae; ddRAD; paleopolyploid; genome skimming; rapid diversification; incongruence.].

Abstract Nucleophosmin ( NPM1 ) is the most commonly mutated gene in acute myeloid leukemia (AML) resulting in aberrant cytoplasmic translocation of the encoded nucleolar protein (NPM1c + ). NPM1c + maintains a unique leukemic gene expression program, characterized by activation of HOXA / B clusters and MEIS1 oncogene to facilitate leukemogenesis. However, the mechanisms by which NPM1c + controls such gene expression patterns to promote leukemogenesis remain largely unknown. Here, we show that the activation of HOXBLINC , a HOXB locus-associated long non-coding RNA (lncRNA), is a critical downstream mediator of NPM1c + -associated leukemic transcription program and leukemogenesis. HOXBLINC loss attenuates NPM1c + -driven leukemogenesis by rectifying the signature of NPM1c + leukemic transcription programs. Furthermore, overexpression of HoxBlinc ( HoxBlinc Tg) in mice enhances HSC self-renewal and expands myelopoiesis, leading to the development of AML-like disease, reminiscent of the phenotypes seen in the Npm1 mutant knock-in ( Npm1 c/+ ) mice. HoxBlinc Tg and Npm1 c/+ HSPCs share significantly overlapped transcriptome and chromatin structure. Mechanistically, HoxBlinc binds to the promoter regions of NPM1c + signature genes to control their activation in HoxBlinc Tg HSPCs, via MLL1 recruitment and promoter H3K4me3 modification. Our study reveals that HOXBLINC lncRNA activation plays an essential oncogenic role in NPM1c + leukemia . HOXBLINC and its partner MLL1 are potential therapeutic targets for NPM1c + AML.