Inflammation contributes to the initiation and disease progression of several lymphoid malignancies. BCR-ABL1-positive B-cell acute lymphoblastic leukemia (BCR-ABL1+ B-ALL) is triggered by the malignant cloning of immature B cells promoted by the BCR-ABL1 fusion gene. However, it is unclear whether the mechanism driving the disease progression of BCR-ABL1+ B-ALL involves inflammatory stimulation. Here, we evaluate BCR-ABL1+ B-ALL cells' response to inflammatory stimuli lipopolysaccharide (LPS) in vitro and in vivo. The results indicate that LPS promotes cell growth and genomic instability in cultured BCR-ABL1+ B-ALL cells and accelerates the BCR-ABL1+ B-ALL development in a mouse model. We show that the LPS-induced upregulation of activation-induced deaminase (AID) is required for the cell growth and disease progression of BCR-ABL1+ B-ALL. Moreover, AID modulates the expression of various genes that are dominated by suppressing apoptosis genes and upregulating DNA damage-repair genes. These genes lead to facilitation for BCR-ABL1+ B-ALL progression. The heat shock protein 90 (Hsp90) inhibitors significantly reduce AID protein level and delay the disease progression of BCR-ABL1+ B-ALL upon inflammatory stimulation. The present data demonstrate the causative role of AID in the development and progression of BCR-ABL1+ B-ALL during inflammation, thus highlighting potential therapeutic targets.
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