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 Blood, 1 July 2007, Vol. 110, No. 1, pp. 339-344.
Prepublished online as a Blood First Edition Paper on March 22, 2007; DOI 10.1182/blood-2006-09-049189.

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NEOPLASIA

Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma

Yan-Yan Liu1, Christophe Leboeuf2, Jing-Yi Shi1, Jun-Min Li1, Li Wang1, Yang Shen1, José-Francisco Garcia3, Zhi-Xiang Shen1, Zhu Chen1, Anne Janin2, Sai-Juan Chen1, and Wei-Li Zhao1

1 State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2 Institut National de la Santé et de la Recherche Médicale (INSERM) U728, Université Paris VII, Institut d'Hématologie, Hôpital Saint Louis, Paris, France; 3 The Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Center (CNIO), Madrid, Spain

The positive regulatory domain I (PRDM1) is a master regulator in the differentiation of mature B lymphocytes to plasma cells. It has 2 isoforms, PRDM1{alpha} and PRDM1ß, and is regulated by the transcriptional regulator nuclear factor kappa (NF)–{kappa}B. PRDM1 protein expression was recently demonstrated in a subset of diffuse large B-cell lymphoma (DLBCL) with aggressive behavior, a type of lymphoma for which rituximab associated with chemotherapy (R-CHOP) is now widely indicated. Using laser microdissection combined with reverse transcription–polymerase chain reaction (RT-PCR) amplification, PRDM1 gene expression was assessed in 82 DLBCL patients. The results showed that both PRDM1{alpha} and PRDM1ß transcripts were expressed in microdissected lymphoma cells only in the non–germinal center B-cell–like (non-GCB) subtype of DLBCL. PRDM1ß gene expression was correlated with short survival time in the non-GCB patients treated with CHOP but not with R-CHOP. In vitro, B-lymphoma cells resistant to chemotherapy expressed PRDM1ß. Rituximab suppressed PRDM1ß expression, which was concomitant with NF-{kappa}B inactivation. The value of PRDM1ß expression as a prognostic marker in non-GCB DLBCL might thus be considered. This study confirms the efficiency of rituximab on DLBCL and allows a better understanding of one of its biologic actions.


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