Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma.
The positive regulatory domain I (PRDM1) is a master regulator in the differentiation of mature B lymphocytes to plasma cells. It has 2 isoforms, PRDM1alpha and PRDM1beta, and is regulated by the transcriptional regulator nuclear factor kappa (NF)-kappaB. 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 PRDM1alpha and PRDM1beta transcripts were expressed in microdissected lymphoma cells only in the non-germinal center B-cell-like (non-GCB) subtype of DLBCL. PRDM1beta 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 PRDM1beta. Rituximab suppressed PRDM1beta expression, which was concomitant with NF-kappaB inactivation. The value of PRDM1beta 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.
Liu
Yan-Yan
YY
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Leboeuf
Christophe
C
Shi
Jing-Yi
JY
Li
Jun-Min
JM
Wang
Li
L
Shen
Yang
Y
Garcia
José-Francisco
JF
Shen
Zhi-Xiang
ZX
Chen
Zhu
Z
Janin
Anne
A
Chen
Sai-Juan
SJ
Zhao
Wei-Li
WL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016328:NF-kappa B; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011241:Prednisone