Ultra-high-scale cytometry-based cellular interaction mapping.

Cellular interactions are of fundamental importance, orchestrating organismal development, tissue homeostasis and immunity. Recently, powerful methods that use single-cell genomic technologies to dissect physically interacting cells have been developed. However, these approaches are characterized by low cellular throughput, long processing times and high costs and are typically restricted to predefined cell types.

Modeling the PAX5P80R Mutation Reveals HIF2α Activation as a Common Feature and Therapeutic Target in B-cell Acute Lymphoblastic Leukemia.

Unlabelled: The transcription factor PAX5 is a major target of genetic alterations in human B-cell precursor acute lymphoblastic leukemia (B-ALL). Among the alterations, the P80R mutation affecting the DNA-binding domain represents the most frequent PAX5 point mutation in B-ALL. In contrast to other somatic PAX5 mutations, PAX5P80R defines a distinct B-ALL subtype characterized by a unique transcriptional program.

GATA2 mutated allele specific expression is associated with a hyporesponsive state of HSC in GATA2 deficiency syndrome.

GATA2 germline mutations lead to a syndrome characterized by immunodeficiency, vascular disorders and myeloid malignancies. To elucidate how these mutations affect hematopoietic homeostasis, we created a knock-in mouse model expressing the recurrent Gata2 R396Q missense mutation. Employing molecular and functional approaches, we investigated the mutation's impact on hematopoiesis, revealing significant alterations in the hematopoietic stem and progenitor (HSPC) compartment in young age.

Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL.

B cell acute lymphoblastic leukemia (B-ALL) is a multistep disease characterized by the hierarchical acquisition of genetic alterations. However, the question of how a primary oncogene reprograms stem cell-like properties in committed B cells and leads to a preneoplastic population remains unclear. Here, we used the PAX5::ELN oncogenic model to demonstrate a causal link between the differentiation blockade, the self-renewal, and the emergence of preleukemic stem cells (pre-LSCs).

Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia-Initiating Cells.

Our understanding of the hierarchical structure of acute leukemia has yet to be fully translated into therapeutic approaches. Indeed, chemotherapy still has to take into account the possibility that leukemia-initiating cells may have a distinct chemosensitivity profile compared to the bulk of the tumor, and therefore are spared by the current treatment, causing the relapse of the disease. Therefore, the identification of the cell-of-origin of leukemia remains a longstanding question and an exciting challenge in cancer research of the last few decades.

PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice.

is a well-known haploinsufficient tumor suppressor gene in human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is involved in various chromosomal translocations that fuse a part of PAX5 with other partners. However, the role of PAX5 fusion proteins in B-ALL initiation and transformation is ill-known. We previously reported a new recurrent t(7;9)(q11;p13) chromosomal translocation in human B-ALL that juxtaposed to the coding sequence of elastin ().