N-terminally truncated FOXP1 protein expression and alternate internal FOXP1 promoter usage in normal and malignant B cells

What is it about?

Smaller FOXP1 proteins are highly abundant in aggressive activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Here we prove our hypothesis that these proteins lack the start of the protein and we have further studied their regulation. We identify a new long form of the protein (FOXP1AL) and identify high level expression of this, and/or short FOXP1, in a rare population of normal B cells. A commonly used ABC-DLBCL cell line (U-2932) containing two distinct tumour cell populations exhibits differential FOXP1 isoform expression and altering the ratio of FOXP1 isoforms affected CD19 expression.

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Why is it important?

We now know that FOXP1 regulation in lymphoma is even more complex than we initially thought. Normal cells that strongly express FOXP1 proteins lacking the typical start of the long protein may help identify the normal cellular counterpart that gives rise to ABC-DLBCL. The ability of FOXP1 to regulate CD19 expression means that it may be possible to manipulate its expression to enhance the activity of therapies targeting CD19 in the clinic. CD19 is also able to regulate signalling via the B-cell receptor, which is a process that is known to be critical for the survival of ABC-DLBCL.