CD34

So it could be that there's a long-term changes in these sinusoidal endothelial cells.

So what we show also that these damage in these sinusoidal endothelial cells have functional consequences, not that they're just damage, but what we wanted to see is how these may affect the homing of primary human CD34 positive that are enriched in stem progenitor cells.

So we took these mice that have been treated with venetoclax and azacitidine, and we injected actually primary CD34 positive cells from umbilical cord blood, normal cells.

And we were looking at the homing after 16 hours, and we were seeing clear degrees in the homing capacity of these cells.

So we did a secondary transplant.

So we leave these CD34 positive and grafted into immunodeficient mice.

We took these cells out after 12 weeks and did secondary transplant to see the long-term effect on the long-term repopulating hematopoietic stem cell, the most primitive population.

And what was quite clear is that the mice that have been treated with venetoclax aza actually have lower long-term hematopoietic stem cell reconstitution in secondary transplant, indicating that this is an implication for potentially bone marrow transplantation of these patients.

Exa-cel in children with transfusion-dependent beta thalassemia or sickle cell disease by Haydar Frangoul from the Sarah Cannon Research Institute at the Children's Hospital at TriStar Centennial, Nashville, and co-authors.

Exagamglogene autotemcel, exa-cel, is a cell therapy in which autologous CD34 hematopoietic cells are engineered through ex vivo CRISPR-Cas9 editing of the erythroid-specific enhancer region of BCL11 to express fetal hemoglobin.

In Phase III studies involving participants 12 to 35 years of age with sickle cell disease or transfusion-dependent beta thalassemia, exa-cel eliminated vaso-occlusive crises and the need for red cell transfusions.

In two ongoing Phase III single-group studies, the investigators evaluated exa-cel in 15 children who were five to 11 years of age with transfusion-dependent beta thalassemia and 11 with sickle cell disease.

We wanna know if these can actually have an impact on infection of mice and disease.

So there's a humanized mouse model of EBV infection where you engraft human CD34-positive, uh, hematopoietic stem cells, uh, into mice.

So you're basically putting, um, precursors, and you can find human B cells, uh, in these mice, and they show that.

And then, uh, they give these mice, once they have the human B cells, they give them, uh, an intraperitoneal injection of the antibodies.

Yes.

When researchers take physical tissue biopsies of these treated areas and perform immunohistochemistry, they stain the tissue to look for specific markers, namely CD34 and CD31.

Which act like biochemical name tags found on the surface of endothelial cells, right? The cells that line blood vessels.

Get it.

When a pathologist looks at the biopsy tissue under a microscope and sees a massive spike in those CD34 and CD31 name tags, it is indisputable physical proof that new capillaries were built.

The cellular blueprint matches the ultrasound imaging.

Which perfectly matches the physical tissue biopsy.

Alternatively, a diagnosis can be made if any three pre-DC markers are present, combined with an absence of expected negative markers.

In BPD-CN, pan T-cell markers should all be negative, such as CD3, pan B-cell markers such as CD19, and myeloid markers such as CD14, CD34, lysozyme, and myeloperoxidase.

While BPD-CN may initially present as skin lesions, pinning down the correct diagnosis often requires cross-functional collaboration among dermatologists, hematologists, oncologists, and pathologists.

Thanks for that really detailed background, Dr. LeBlanc.