Molecular genetics of peripheral T-cell lymphomas

Abstract

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.

The Comparative Diagnostic Features of Canine and Human Lymphoma

“…Based upon their morphological, genetic, and immunophenotypic heterogeneity, it is accepted that PTCL, NOS contains many different unique entities, however no reliable criteria have been established that allow for consistent identification of any one specific entity. In both human and canine, peripheral T-cell lymphoma not-otherwise specified (PTCL, NOS) is the most common T-cell lymphoproliferative disease, representing approximately 30% and 39%–65% of all human and canine cases, respectively [11,13,51]. However, as a percentage of all forms of lymphoma, PTCL, NOS is uncommon in humans, representing less than 1% of all NHL, but comparatively much more common in dogs, at 15% of all lymphomas.…”

“…The cellular origins of both human PTCL, NOS (hPTCL, NOS) and cPTCL, NOS are likely heterogeneous, but are presumed to be derived from post-thymic T-cells in various stages of transformation [51]. Gene expression profiling (GEP) studies suggest that hPTCL, NOS can be subdivided into at least three cell-of-origin subgroups, namely cytotoxic, helper, and follicular helper PTCL, NOS [52,53].…”

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

“…Within this rather rare disease group, the most common subtype is PTCL-not otherwise specified (NOS), which summarizes cases not attributable to other entities, followed by angioimmunoblastic T-cell lymphoma (AITL), ALK + anaplastic large cell lymphoma (ALCL), and ALK − ALCL [46,48,49]. Further subtypes include adult T-cell lymphoma/leukemia (ATLL), T-cell prolymphocytic leukemia (T-PLL), and cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and Sézary syndrome (SS) [50,51]. The only frequent recurring chromosomal translocation identified in the PTCLs is the t(2;5)(p23;q35) NPM-ALK fusion characteristic of ALK + ALCL.…”

“…High-throughput methodologies were used to identify the cell of origin and to characterize commonly altered pathways in PTCL [51,59–67]. These efforts were successful in defining characteristic gene expression profiles for AITL, ALK + ALCL, ATLL, and PTCL-NOS, identifying recurrent mutations and recognizing specific subtypes, which can now help to support correct diagnosis and classification of patients to distinct disease subgroups with different prognoses [46,59,60,62,63].…”

SNPs Array Karyotyping in Non-Hodgkin Lymphoma

“…The latter, however, mainly consist in very aggressive behavior and poor clinical outcome for most nodal tumors [77,78]. As the majority of PTCLs cannot be currently classified within a specific group based on morphology, phenotype, genetics and clinical features, they were included within the not otherwise specified group (PTCL/NOS) [79].…”