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Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing
TLDR
It is demonstrated that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4).
Ott1(Rbm15) has pleiotropic roles in hematopoietic development
TLDR
Data show a requirement for Ott1 in B lymphopoiesis, and inhibitory roles in the myeloid, megakaryocytic, and progenitor compartments, and the ability of Ott1 to affect hematopoietic cell fate and expansion in multiple lineages is a novel attribute for a spen family member and delineates Ott1 from other known effectors of hematopolietic development.
The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model.
TLDR
It is established that concomitant activation of RBPJ (Notch signaling) and MPL (cytokine signaling) transforms cells of the megakaryocytic lineage and suggest that specific targeting of these pathways could be of therapeutic value for human AMKL.
STAT5 is crucial to maintain leukemic stem cells in acute myelogenous leukemias induced by MOZ-TIF2.
TLDR
The data suggest that STAT5AB is required for the self-renewal of LSCs and represents a combined signaling node of FLT3-ITD and MOZ-TIF2 driven leukemogenesis, and targeting aberrantly activated STAT5 or rewired downstream signaling pathways may be a promising therapeutic option.
Hematopoietic stem cells lacking Ott1 display aspects associated with aging and are unable to maintain quiescence during proliferative stress.
TLDR
It is shown, specifically under replicative stress, that Ott1-deleted HSCs have a significant reduction of the G(0) cell-cycle fraction associated with self-renewal and undergo early failure, establishing a requirement for Ott1 in stress hematopoiesis and suggesting thatOtt1-dependent processes may converge with those affected by aging.
In Vivo Association of v-Abl with Shc Mediated by a Non-phosphotyrosine-dependent SH2 Interaction (*)
TLDR
It is shown that Shc is tyrosine-phosphorylated and associates with Grb2 in v-Abl-transformed cells, whereas Shc in NIH3T3 cells is phosphorylated solely on serine and is not Grb 2-associated.
Ott1 (Rbm15) Is Essential for Placental Vascular Branching Morphogenesis and Embryonic Development of the Heart and Spleen
TLDR
This outcome showed that the process of vascular branching morphogenesis in Ott1-deficient animals was regulated by the trophoblast compartment rather than the fetal vasculature, and may also be important for the pathogenesis of placental insufficiency and cardiac malformations.
CD44 induced enhancement of phosphatase activity and calcium influx: Modifications of EGR-1 expression and cell proliferation
TLDR
It is proposed that the enhanced phosphatase activity in theCD44 cells increased the dephosphorylation rate of Akt; at the same time, the increased intracellular concentration of Ca2+ in the CD44 cells ensured that the phosphorylation ofAkt remains intact albeit at lower concentrations as compared with the vector control.
Rapid and Robust Mobilization of CD34+ HSCs without G-CSF Following Administration of Mgta-145 Alone or in Combination with Plerixafor
TLDR
A Phase 1 dose-escalating study to evaluate the safety, PK and PD of MGTA-145 as a single agent and in combination with plerixafor was well tolerated and a significant increase in fold change relative to baseline in CD34+ cells was shown.
Expression of CD25 independently predicts early treatment failure of acute myeloid leukaemia (AML)
TLDR
High CD25 expression at diagnosis in young (<60 years) AML patients in retrospective analysis correlated with a significantly shorter overall survival (OS) and relapse-free survival (RFS) and double positive patients had the poorest OS and RFS.
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