Molecular genetics of peripheral T-cell lymphomas.
Peripheral T-cell lymphomas (PTCL) are rare neoplasms that in most instances respond poorly to conventional chemotherapies. Four varieties--PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK+ anaplastic T-cell lymphoma (ALCL), and ALK- ALCL--account for about 60 % of them. Their classification is difficult because of the wide spectrum of morphologic features and the lack of robust immunohistochemical markers. Thus, high-throughput technologies can importantly contribute to their better understanding. In particular, gene expression profiling has cleared the borders among PTCL/NOS, ALK- ALCL and AITL. In fact, gene signatures have been developed even from formalin-fixed paraffin-embedded tissue samples that definitely distinguish one tumor from the other(s). This has important practical implications: for instance on routine diagnostics PTCL/NOS expressing CD30 can be easily confused with ALK- ALCL, but has a much worse prognosis. Therefore, the clear-cut distinction between the two conditions is pivotal to understand the results of ongoing trials with Brentuximab Vedotin, targeting the CD30 molecule. Besides improving the diagnosis, molecular studies have provided the rationale for the usage of novel drugs in the setting of PTCLs, such as ALK inhibitors in ALK+ ALCL, anti-angiogenetic drugs in AITL, and tyrosine kinase inhibitors in PTCL/NOS and ALK+ and ALK- ALCLs.
Hematopathology Unit, Department of Experimental, Diagnostic, and Specialty Medicine, S. Orsola-Malpighi Hospital, Pavillon 8, Bologna University Medical School, Via Massarenti, 9, 40138, Bologna, Italy, pierpaolo.piccaluga@unibo.it.
Pier Paolo
PP
Piccaluga
Valentina
V
Tabanelli
Stefano A
SA
Pileri
D018951:Antigens, CD20; D000970:Antineoplastic Agents / Q000627:therapeutic use; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000145:classification* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D058990:Molecular Targeted Therapy; D016328:NF-kappa B; D051562:Proto-Oncogene Proteins c-bcr; D059467:Transcriptome
D018951:Antigens, CD20; D000970:Antineoplastic Agents; D016328:NF-kappa B; D051562:Proto-Oncogene Proteins c-bcr