Finding one disease is actually many: Diffuse large B-cell lymphomas

2000

Challenge

Some patients with diffuse large B-cell lymphomas (DLBCL) live longer and respond better to therapy than others, highlighting an urgent need to better understand the disease’s underlying biology and inform more effective treatment approaches.

Advance

IRP researchers led by Louis Staudt, M.D., Ph.D., profiled the genes expressed in patients with DLBCL and found important differences, leading to the identification of three new molecularly and clinically distinct subclasses of the disease: germinal center B-cell-like, activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL).

Impact

These discoveries revealed new molecular targets based on each subclass and informed the development of new therapies. For example, the discovery that one subgroup of DLBCL relies on the NF-kB signaling pathway allowed physicians to target that pathway directly, leading to complete remission in a number of cases.

Publications

Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 403(6769), 503-11.

Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM. (2003). A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphomaProc Natl Acad Sci U S A. 100(17), 9991-6.