Deciphering impact of B-cell precursor acute lymphoblastic leukemia bone marrow microenvironment on immune cell function

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells residing in the bone marrow modulate supportive cells to create a leukemic niche facilitating their own persistence. Elucidating the influence of leukemic niche formation on immune cells is essential to assess its impact on cell-based immunotherapies. We performed mono- and co-cultures of mesenchymal stromal cells (MSCs) and ALL cells to assess changes in gene expression upon co-culture. Total-RNA sequencing revealed an interferon a/b (IFNa/b)-related gene signature in MSCs upon co-culture with ALL compared to mono-culture, which is ETV6::RUNX1-subtype linked. However, ALL cell viability and chemotherapy resistance were not affected upon inhibition of IFN signaling. Secretome analysis revealed upregulation of pro-inflammatory cytokines, and chemokines such as CCL4, CXCL5, CXCL8, and CXCL10 in the leukemic niche. We will assess gene expression changes in other bone marrow supportive cell types upon co-culture with ALL cells. The influence of the leukemia-induced IFNa/b gene signature in bone marrow supportive cells on the response to immunotherapy, such as blinatumomab, is currently being studied.

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Artikel online veröffentlicht:
09. Mai 2025