Wanted: Prospective Studies of Alternative Donors

Minimal Residual Disease following Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia Lineage-Specific Chimerism Analysis and Molecular Monitoring Improve Outcome of Donor Lymphocyte Infusions

Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients

Myelodysplastic syndrome: An inability to appropriately respond to damaged DNA?

CMV Infection after Transplant from Cord Blood Compared to Other Alternative Donors: The Importance of Donor-Negative CMV Serostatus

Sirolimus as Primary Treatment of Acute Graft-versus-Host Disease following Allogeneic Hematopoietic Cell Transplantation

Are transplantable stem cells required for adult hematopoiesis?

Clinical Applications for Biomarkers of Acute and Chronic Graft-versus-Host Disease

Development and Validation of a Test Dose Strategy for Once-Daily i.v. Busulfan: Importance of Fixed Infusion Rate Dosing

Feasibility and Safety of Adoptive Immunotherapy with CIK Cells after Cord Blood Transplantation

We have reconstituted human mitochondrial transcription in vitro on DNA oligonucleotide templates representing the light strand and heavy strand-1 promoters using protein components (RNA polymerase and transcription factors A and B2) isolated from Escherichia coli. We show that 1 eq of each transcription factor and polymerase relative to the promoter is required to assemble a functional initiation complex. The light strand promoter is at least 2-fold more efficient than the heavy strand-1 promoter, but this difference cannot be explained solely by the differences in the interaction of the transcription machinery with the different promoters. In both cases, the rate-limiting step for production of the first phosphodiester bond is open complex formation. Open complex formation requires both transcription factors; however, steps immediately thereafter only require transcription factor B2. The concentration of nucleotide required for production of the first dinucleotide product is substantially higher than that required for subsequent cycles of nucleotide addition. In vitro, promoter-specific differences in post-initiation control of transcription exist, as well as a second rate-limiting step that controls conversion of the transcription initiation complex into a transcription elongation complex. Rate-limiting steps of the biochemical pathways are often those that are targeted for regulation. Like the more complex multisubunit transcription systems, multiple steps may exist for control of transcription in human mitochondria. The tools and mechanistic framework presented here will facilitate not only the discovery of mechanisms regulating human mitochondrial transcription but also interrogation of the structure, function, and mechanism of the complexes that are regulated during human mitochondrial transcription.

Emergency IVF versus ovarian tissue cryopreservation: decision making in fertility preservation for female cancer patients

Electrocardiographic features of patients with COVID-19: One year of unexpected manifestations

PML-RARα/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia

Here, we report the identification of the RNA binding motif protein RBM15B/OTT3 as a new CDK11(p110) binding partner that alters the effects of CDK11 on splicing. RBM15B was initially identified as a binding partner of the Epstein-Barr virus mRNA export factor and, more recently, as a cofactor of the nuclear export receptor NXF1. In this study, we found that RBM15B co-elutes with CDK11(p110), cyclin L2α, and serine-arginine (SR) proteins, including SF2/ASF, in a large nuclear complex of ∼1-MDa molecular mass following size exclusion chromatography. Using co-immunoprecipitation experiments and in vitro pulldown assays, we mapped two distinct domains of RBM15B that are essential for its direct interaction with the N-terminal extension of CDK11(p110), cyclin L2α, and SR proteins such as 9G8 and SF2/ASF. Finally, we established that RBM15B is a functional competitor of the SR proteins SF2/ASF and 9G8, inhibits formation of the functional spliceosomal E complex, and antagonizes the positive effect of the CDK11(p110)-cyclin L2α complex on splicing both in vitro and in vivo.