Publications by authors named "Klaudia Galant"

Hematopoiesis develops in the bone marrow (BM) where multiple interactions regulate the differentiation and preservation of hematopoietic stem and progenitor cells (HSPCs). Immune-deficient murine models have enabled the analysis of molecular and cellular regulation of human HSPCs, but the physiology of these models is questioned as human hematopoietic cells develop in xenogenic microenvironments. In this study, we thoroughly characterized a humanized (h) in vivo BM model, developed from fetal (F/) and post-natal (P-N/) mesenchymal stromal cell (MSC) differentiation (called hOssicles [hOss]), in which human hematopoietic cells are generated following the transplantation of CD34 cells.

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Pediatric acute myeloid leukemia frequently harbors fusion oncogenes associated with poor prognosis, including KMT2A, NUP98, and GLIS2 rearrangements. Although murine models have demonstrated their leukemogenic activities, the steps from a normal human cell to leukemic blasts remain unclear. Here, we precisely reproduced the inversion of chromosome 16 resulting in the ETO2::GLIS2 fusion in human induced pluripotent stem cells (iPSCs).

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Article Synopsis
  • The study investigates the role of the ETO2::GLIS2 fusion oncogene in pediatric acute myeloid leukemia (AML), highlighting its connection to worse outcomes in patients.
  • The researchers developed models using lentiviral transduction and CRISPR-Cas9 to explore how ETO2::GLIS2 influences leukemia development in human fetal versus post-natal hematopoietic stem cells.
  • They found that the presence of specific human cytokines like IL3 and SCF is crucial for leukemogenesis, suggesting that a combination treatment targeting MEK and BCL2 could effectively reduce leukemia progression.
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