ISAL 2025 | The functional and phenotypical heterogeneity of leukemic cells infiltrating organs in AML

Yes, so many reports have characterized and reported about the infiltration of solid organs by leukemic cells. However, the meaning of these infiltrations, apart from those of chloromas, that are particularly skin infiltrations, is not really known. So we were interested to know what is the meaning of, what is the feature of this blast from specific organs, and how they respond to therapy, particularly, and how they play a role in the relapse of disease. So we took a mouse model which is based on MLL-AF9 translocation, which is very well characterized and very known. So we isolated the blast cells from the organs of these mice and treated them in vitro and characterized them phenotypically. So at the immunophenotype level, they still express leukemic stem cell features, but they also expressed different markers for myeloid cells and adhesion molecules like CD44 and CD11B. So we then performed clonogenic assays to assess their capacity to self-renew and build up colonies in the presence of treatment. And we found that all these blasts from different organs, they are also aggressive in their growth and their response to therapy. Particularly, cells from the liver, they were particularly resistant to treatment with targeted therapies and also with chemotherapy as previously reported. So we are now planning to do serial transplantations to assess the leukemogenicity of these cells from different organs and also from patients. Of course, we are extending our analysis on autopsy materials, performing special transcriptomics, and also we plan to isolate cells from liquor, so cerebrospinal fluid, and skin biopsies from patients to perform in vitro assays and also xenotransplant and treat them in comparison to the counterpart of the bone marrow cells.

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