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  • P-III-0992

Insight into communication mechanisms in MLL-rearranged Leukemia

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Cell Biology Insights

Poster

Insight into communication mechanisms in MLL-rearranged Leukemia

Topic

  • Cell Biology Insights

Authors

Joanna Watral (Lund / SE), Sudip Ghosh (Lund / SE), Ariana Seira Calderon Moreno (Lund / SE), Mina Davoudi (Lund / SE), Qinyu Zhang (Lund / SE), Maria Jassinskaja (Lund / SE), David Bryder (Lund / SE), Charlotta Böiers (Lund / SE), Jenny Hansson (Lund / SE)

Abstract

Although much progress has been made in the treatment of some types of blood cancers, others, particularly leukemias associated with MLL rearrangements, are still associated with dismal prognosis in both children and adults. New therapeutic options that are tailored to the age-specific biology of the disease are urgently needed. While numerous intrinsic age-specific molecular features of leukemia-initiating cells have been identified, understanding the interactions between leukemic cells and their microenvironment remains far from comprehensive. The aim of this study was to establish methods to investigate proteomic and cellular changes to the local extracellular microenvironments of hematopoietic stem and progenitor cells upon leukemia initiation.Biological materials were isolated from mice with an inducible MLL oncogene system and fusion partners. Flow cytometry and proteomic analysis were used to monitor changes in the fetal liver and adult bone marrow leukemic microenvironments. For ex vivo studies, polyvinyl alcohol-based (PVA) culture system was used. Proteomics data were acquired using FAIMSPro coupled to Exploris 480 in DIA mode, followed by statistical and bioinformatic analysis to elucidate potential communication mechanisms between leukemic cells and their environment.We established a protocol to study the proteomic composition of secretome using a PVA culture system and noticed marked differences in the fetal and adult pre-leukemic cells’ potential to influence and communicate with their microenvironment. While adult hematopoietic progenitors increase their secretion upon leukemia induction, fetal cells instead suppress secretion. Additionally, we found that the secretion pattern could be reversed by treatment with proteins that are highly abundant in the normal extracellular fluids of the niche. However, these changes were more specific to adult cells compared to their fetal counterpart. The findings indicate that adult pre-leukemic cells more actively communicate with and influence the microenvironment, showing greater vulnerability to reversion of changes occurring upon leukemia initiation compared to fetal cells. These differences highlight significant variations in disease biology between infant and adult leukemias, offering insights for improving age-tailored therapeutic approaches to enhance the outcomes for leukemia patients.
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