Anti-NPM1 monoclonal antibody, clone 2053DU6.3.2

Nucleophosmin (NPM1) is an abundant nucleolar protein that aids in the maturation of pre-ribosomal particles and participates in oncogenic stress responses through its interaction with the Alternative Reading Frame tumor suppressor (p14ARF). NPM1 mediates multiple mechanisms of phase separation which contribute to the liquid-like properties of nucleoli. However, the effects of phase separation on the structure and dynamics of NPM1 are poorly understood. Here we show that NPM1 undergoes phase separation with p14ARF in vitro, forming condensates that immobilize both proteins. We probed the structure and dynamics of NPM1 within the condensed phase using solid-state NMR spectroscopy. Our results demonstrate that within the condensed phase, the NPM1 oligomerization domain forms an immobile scaffold, while the central intrinsically disordered region and the C-terminal nucleic acid binding domain exhibit relative mobility. (C) 2019 Elsevier Inc. All rights reserved.

Epithelial growth factor-like 7 (EGFL7) is a secretory protein with a well-characterized role in angiogenesis and the oncogenesis of certain solid tumors. Overexpression of EGFL7 is associated with adverse prognosis in patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, whether this association persists after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To further clarify the prognostic role of EGFL7, seventy-one AML patients with EGFL7 expression data who underwent allo-HSCT from The Cancer Genome Atlas database were included and divided into either EGFL7(high) or EGFL7(low) group based on the median EGFL7 expression level. Two groups had similar clinical and molecular characteristics except that the EGFL7(high) group had less frequent NPM1 mutations (P= .001). Kaplan-Meier survival curves showed that high EGFL7 expressers had shorter OS than the low expressers (P= .040). Univariate analysis showed that high EGFL7 expression, MLL-PTD, RUNX1 and TP53 mutations were associated with short OS (all P< .05). Multivariate analysis indicated that high EGFL7 expression, FLT3-ITD, RUNX1 and TP53 mutations were independent risk factors for OS (all P< .05). Collectively, our study suggested that EGFL7, like the other widely-used risk stratification factors, could serve as a prognostic tool and therapeutic target in AML, even after allo-HCST.