To estimate the distribution of lymphoid neoplasms in China, we conducted a comprehensive analysis, based on subtype, age, sex, and lesion, of primary and resected biopsy specimens of 4,638 lymphoid neoplasms diagnosed from 2004 to 2008 at 5 large hospitals. Of the 4,638 patients, mature B-cell neoplasms accounted for 64.3% of all lymphoid neoplasms, mature T/NK-cell neoplasms for 23.3%, and Hodgkin lymphoma for 8.6%. The most common subtype was diffuse large B-cell lymphoma (36.2%), followed by extranodal NK/T-cell lymphoma, nasal type (11.0%), classic Hodgkin lymphoma (8.4%), extranodal marginal zone B-cell lymphoma (7.7%), plasmacytic neoplasm (5.0%), and peripheral T-cell lymphoma, not otherwise specified (3.9%). For most lymphoid neoplasm subtypes, male subjects showed higher rates than female subjects. In summary, our study showed that the epidemiologic features of lymphoid neoplasms in China are distinct from those in Western countries and similar in many ways to those in other countries of the Far East.
Key Points Well-defined miRNA signatures for normal B-cell subsets and their malignant counterparts including BL and DLBCL subgroups were identified. In DLBCL, miRNA-155 expression is associated with R-CHOP resistance, but in vitro sensitivity to AKT pathway inhibition.
• Anaplastic large-cell lymphoma has a unique miRNA signature.• The miR-17;92 is an important downstream effector of ALK oncogenic pathway.Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[1]) ALCLs, 25 ALK-negative (ALK[2]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(1) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(1) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17∼92 cluster and its paralogues were also highly expressed in ALK(1) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.
miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNA classifier showed consistent results in formalin-fixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.
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