Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets.

Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology.

Deciphering Acute Myeloid Leukemia Associated Transcription Factors in Human Primary CD34+ Hematopoietic Stem/Progenitor Cells.

Hemato-oncological diseases account for nearly 10% of all malignancies and can be classified into leukemia, lymphoma, myeloproliferative diseases, and myelodysplastic syndromes. The causes and prognosis of these disease entities are highly variable. Most entities are not permanently controllable and ultimately lead to the patient's death.

Combined proteomics and CRISPR‒Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo.

Background: Acute leukemias represent deadly malignancies that require better treatment. As a challenge, treatment is counteracted by a microenvironment protecting dormant leukemia stem cells.

Methods: To identify responsible surface proteins, we performed deep proteome profiling on minute numbers of dormant patient-derived xenograft (PDX) leukemia stem cells isolated from mice.

Defined Human Leukemic CD34+ Liquid Cultures to Study HDAC/Transcriptional Repressor Complexes.

Defined human primary cell model systems with growth dependence on oncogenes are highly requested to investigate tumor pathogenesis and to validate pharmacological inhibitors that specifically target oncoproteins and their executing protein complex partners. In acute myeloid leukemia (AML), transcription factors such as RUNX1 and MLL1, which are important for normal blood cell development, frequently harbor mutations including chromosomal translocations with other coding genes, resulting in tumor-promoting gain-of-function fusion proteins. These oncoproteins completely modify transcriptional programs, thereby inducing malignant cell phenotypes.