Qiusheng Chen

The prognostic value of immunohistochemical subtyping in Chinese patients with de novo diffuse large B-cell lymphoma undergoing CHOP or R-CHOP treatment

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognised variability in molecular aetiology and clinical outcome. Though the use of agents such as rituximab significantly improves outcome, intrinsic genetic and morphological factors greatly affect the response to treatment. The objective of this study was to evaluate the prognostic value of immunohistochemical subtyping and the International Prognostic Index (IPI) for predicting treatment outcome in Chinese DLBCL patients. We followed 108 cases of DLBCL and performed prognostic analyses based on molecular subtyping of the disease through immunostaining of tissue samples. The use of rituximab conferred a clinical benefit to DLBCL patients regardless of disease subtype. Importantly, this treatment regimen also improved outcomes in patients with the non-germinal centre B-cell-like (GCB) DLBCL subtype, frequently associated with poorer prognosis. Our results suggest that IPI was the best tool for the prediction of treatment outcome in our patient cohort, regardless of treatment regimen. Furthermore, the use of rituximab alongside classical chemotherapy regimens can improve the outcomes for DLBCL patients who exhibit both GCB and non-GCB subtypes of the disease.

The 12-year follow-up of survival, chronic adverse effects, and retention of arsenic in patients with acute promyelocytic leukemia

To the editor: Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) have demonstrated notable success in the treatment of acute promyelocytic leukemia (APL).[1][1][⇓][2]-[3][3] However, few studies have reported the adverse effects (AEs), long-term toxicity, and secondary carcinogenesis of

All-trans retinoic acid and arsenic combination therapy benefits low-to-intermediate-risk patients with newly diagnosed acute promyelocytic leukaemia: a long-term follow-up based on multivariate analysis

All-trans retinoic acid (ATRA) and chemotherapy have enabled great improvements in the treatment of acute promyelocytic leukaemia (APL). High initial white blood cell (WBC) and low platelet counts are generally considered as independent risk factors for APL (Sanz et al, 2000). However, the relapse rate has been reported to be as high as 5–30% (Tallman, 2007). In 2001, a pilot clinical trial was held at Shanghai Institute of Haematology to treat APL with ATRA and arsenic combination therapy (Shen et al, 2004), and the 5-year follow-up (Hu et al, 2009) showed high efficacy. Since then, this approach has been shown not to be inferior to or even better than ATRA and chemotherapy. In the present study, we updated the follow-up to clarify the long-term survival and the risk factors in APL patients when using the ATRA and arsenic combination therapy. Between February 2001 and July 2010, 217 newly diagnosed APL patients were included in this study. Informed consent was obtained in all patients. The criteria for diagnosis, cytogenetic analysis and molecular tests for PML-RARA transcripts were performed as previously described (Shen et al, 2004), together with the treatment protocol (Table SI). Briefly, for induction therapy, all patients received ATRA and arsenic until documented complete remission (CR). Idarubicin (IDA) was given in case of high-risk patients. Three courses of consolidation therapy followed induction. The maintenance therapy consisted of 5 cycles of sequential use of ATRA, arsenic and low-dose chemotherapy (6-mercaptop-

Novel STAT5B-RARA fusion transcript in acute promyelocytic leukemia: identification and treatment response.

1Department of Hematology, Bei Zhan Hospital, Shanghai, China, 2State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China, 3Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu Province, China and 4Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival

Acute myeloid leukemia (AML) with an NPM1 mutation (NPMc+) has a distinct gene expression signature and displays molecular abnormalities similar to mixed lineage leukemia (MLL), including aberrant expression of the PBX3 and HOXA gene cluster. However, it is unclear if the aberrant expression of PBX3 and HOXA is essential for the survival of NPM1-mutated leukemic cells. Methods: Using the gene expression profiling of TCGA and E-MTAB-3444 datasets, we screened for high co-expression of PBX3 and HOXA9 in NPMc+ leukemia patients. We performed NPMc+ depletion and overexpression experiments to examine aberrant H3K79 methylation through epigenetic regulation. Through RNA interference technology and small-molecule inhibitor treatment, we evaluated the effect of methyl-modified H3K79 on cell survival and explored the possible underlying mechanism. Results: We showed that NPMc+ increased the expression of PBX3 and HOXA9, which are both poor prognosis indicators in AML. High PBX3 and HOXA9 expression was accompanied by increased dimethylated and trimethylated H3K79 in transgenic murine Lin-Sca-1+c-Kit+ cells and human NPMc+ leukemia cells. Using chromatin immunoprecipitation sequencing (ChIP-seq) assays of NPMc+ cells, we determined that hypermethylated H3K79 was present at the expressed HOXA9 gene but not the PBX3 gene. PBX3 expression was positively regulated by HOXA9, and a reduction in either PBX3 or HOXA9 resulted in NPMc+ cell apoptosis. Importantly, an inhibitor of DOT1L, EPZ5676, effectively and selectively promoted NPMc+ human leukemic cell apoptosis by reducing HOXA9 and PBX3 expression. Conclusion: Our data indicate that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor.