PANE1 Potential Therapeutic Target in CLL

[Guest guest]

Blood First Edition Paper, prepublished online January 3, 2006

Submitted August 30, 2005

Accepted December 20, 2005

The PANE1 gene encodes a novel human minor histocompatibility antigen

that is selectively expressed in B-lymphoid cells and B-CLL

G Brickner, et.al.

Minor histocompatibility antigens (mHAg) are peptides encoded by

polymorphic genes that are presented by MHC molecules and recognized

by T cells in recipients of allogeneic hematopoietic cell

transplants. Here we report that an alternative transcript of the

proliferation associated nuclear element 1 (PANE1) gene encodes a

novel HLA-A*0301-restricted mHAg that is selectively expressed in B-

lymphoid cells.

The antigenic peptide is entirely encoded within a unique exon not

present in other PANE1 transcripts. Sequencing of PANE1 alleles in

mHAg-positive and mHAg-negative cells demonstrates that differential

T cell recognition is due to a single nucleotide polymorphism within

the variant exon that replaces an arginine codon with a translation

termination codon.

The PANE1 transcript that encodes the mHAg is expressed at high

levels in resting CD19+ B cells and B-lineage chronic lymphocytic

leukemia (B-CLL) cells, and at significantly lower levels in

activated B cells. Activation of B-CLL cells through CD40L

stimulation decreases expression of the mHAg-encoding PANE1

transcript and reciprocally increases expression of PANE1 transcripts

lacking the mHAg-encoding exon.

These studies suggest distinct roles for different PANE1 isoforms in

resting compared with activated CD19+ cells, and identify PANE1 as a

potential therapeutic target in B-CLL.