Cutaneous Anaplastic Large Cell Lymphoma and Peripheral T-Cell Lymphoma NOS Show Distinct Chromosomal Alterations and Differential Expression of Chemokine Receptors and Apoptosis Regulators

Abstract

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) has an indolent clinical course and favorable prognosis. On the contrary, primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTL-NOS) shows aggressive clinical behavior. To identify genomic events relevant in the pathogenesis of these cutaneous T-cell lymphomas (CTCLs), we carried out array-based comparative genomic hybridization (CGH) analysis. Simultaneously, gene expression profiling was conducted to gain insight into gene expression programs associated with the different clinical behavior of these CTCLs. C-ALCL was characterized by gains on chromosome 7q and 17q and losses on 6q and 13q. PTL-NOS similarly showed gains on 7q and 17q, but was distinguished by gains on chromosome 8 and loss of a focal overlapping region on 9p21. We identified minimal common regions harboring candidate oncogenes and tumor suppressor genes in C-ALCL and PTL-NOS. Genes with a role in lymphocyte chemotaxis, apoptosis, and proliferation were overrepresented among genes differentially expressed between these lymphomas. C-ALCL showed higher expression of the skin-homing chemokine receptor genes CCR10 and CCR8, which may explain the lower tendency to disseminate to extracutaneous sites. Furthermore, C-ALCL and PTL-NOS showed aberrant expression of distinct genes implicated in apoptosis and proliferation, such as IRF4/MUM1 and PRKCQ, which may account for differences in clinical aggressiveness.

Mucosal CD30-positive T-cell lymphoproliferations of the head and neck show a clinicopathologic spectrum similar to cutaneous CD30-positive T-cell lymphoproliferative disorders

“…The existence of patients with mucocutaneous disease suggests mucosal CD30-positive T-cell lymphoproliferations may be biologically similar to cutaneous cases, possibly reflecting molecular features contributing to epitheliotropism of the CD30-positive T cells. 33 Oral involvement in patients with cutaneous mycosis fungoides typically occurs late in the clinical course and is associated with poor prognosis. 26 Our patient with mycosis fungoides (case 8) died of unrelated causes 19 months after presentation with disease in the nasal cavity, at which time he had persistent cutaneous disease but no evidence of mucosal disease.…”

Telomerase functions beyond telomere maintenance in primary cutaneous T-cell lymphoma

“…11,[37][38][39] Indeed, data from our group 22,27 and from others [23][24][25][26]28,29,[40][41][42][43] showed the presence of more complex chromosome aberrations in aggressive CTCL than in C-ALCL. 28,44 When telomeres become critically short, it is believed that their protective function is compromised and that cells follow the flow diagram process (Figure 7) with replicative senescence, crisis, escape from crisis, and maintenance of TL. 45 Our data support this theoretical process and also suggest that aggressive CTCLs are passed-over crisis cells.…”

“…To answer this question, genomic abnormalities were investigated in SS patient cells and cell lines, taking into consideration chromosome aberrations previously reported in SS patients by our group 27 and others. [23][24][25][26]28,29 For cases 2 and 17, AU (data not shown), c-MYC and centromere 8 fluorescent probes were chosen to investigate SS nuclei chromosomal status in combination with antibodies to delineate SS cells ( Figure 2E-H) or with peptide nucleic acid telomeric probes to evaluate TL ( Figure 2I-J). Image analysis revealed that abnormal chromosome content was restricted to both neoplastic SS T cells ( Figure 2E-H) and to nuclei with short telomeres, whereas cells with normal chromosome content showed long telomeres ( Figure 2I-J).…”

“…21 In these lymphoproliferations, the neoplastic T cells involve the skin as a primary site, but with disease progression, abnormal cells may also infiltrate blood, lymph nodes, lungs, heart, liver, and spleen, except for SS, which arises suddenly as an aggressive leukemic variant. 21 Whereas recent cytogenetic studies on T-MF, SS, and C-ALCL reported the presence of genetic aberrations, [22][23][24][25][26][27][28][29] the key molecular targets underlying CTCL pathogenesis remain elusive. This lack of insight into the biology of CTCL has hindered the development of true targeted therapies.…”

Genetic alterations in systemic nodal and extranodal non‐cutaneous lymphomas derived from mature T cells and natural killer cells

“…The abnormalities of ALKÀALCL do not fully overlap with whose reported for other T-cell neoplasms, but can be shared with primary cutaneous ALCL. (11,45,57,58) The last observation is intriguing, indicating a high similarity between these two types, despite their diverse clinical features and outcomes, with a much better prognosis observed for primary cutaneous ALCL. (59) Two translocations have been recently reported in ALKÀALCL.…”