Disease relevance of TSPYL2

• HLA-G message was present in all cutaneous B-cell (CBCL) and T-cell (CTCL) lymphomas evaluated [1].
• These studies show that S aureus containing superantigen enterotoxins are commonly found in patients with CTCL especially individuals with erythroderma where they could exacerbate and/or perpetuate stimulate chronic T-cell expansion and cutaneous inflammation [2].
• Thirty-nine patients with cutaneous T cell lymphoma (CTCL; including mycosis fungoides or the Sezary syndrome) with no previous treatment other than topical therapy or oral corticosteroids, received total skin electron beam irradiation (TSEB) and either sequential or simultaneous systemic chemotherapy [3].
• PATIENTS AND METHODS: Sixty-one patients with measurable or assessable lymphoproliferative disorders (31 stage III or IV low-grade NHL; 21 chronic lymphocytic leukemia [CLL]; and nine cutaneous T-cell NHL [CTCL]) were enrolled [4].
• Cytogenetic abnormalities that could play a role in CD30+ CTCL tumour pathogenesis and relapses remain unknown [5].

High impact information on TSPYL2

• While in CBCL mostly indolent types displayed HLA-G positivity, in CTCL HLA-G expression was associated with high-grade histology and advanced stage of the disease [1].
• Analysis of the T-cell receptor V beta repertoire in 14 CTCL patients found that only 4 had the expected monoclonal expansion of a specific V beta gene, whereas 10 had oligoclonal or polyclonal expansion of several V beta families [2].
• Overexpression of hCINAP in HeLa cells results in a decrease in the average number of Cajal bodies per nucleus, consistent with it affecting either the stability of Cajal bodies and/or their rate of assembly [6].
• The hCINAP protein sequence is highly conserved across its full-length from human to plants and yeast and is ubiquitously expressed in all human tissues and cell lines tested [6].
• The yeast orthologue of CINAP is a single copy, essential gene [6].

Chemical compound and disease context of TSPYL2

• We present a case of a patient who developed all manifestations of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) acutely following treatment of cutaneous T-cell lymphoma (CTCL, Sezary syndrome) with deoxycoformycin (pentostatin) [7].
• Bexarotene and systemic disease progression in CTCL [8]?
• While treating the stage III CTCL with polychemotherapy, we used an active colloidal hydrogel topically to manage wound healing and to treat and prevent potential sources of sepsis [9].

Biological context of TSPYL2

• However, hCINAP and TAFIID32 mRNAs are translated from different ATG codons and use distinct reading frames, resulting in them having no identity in their respective protein sequences [6].
• SET-related cell division autoantigen-1 (CDA1) arrests cell growth [10].
• We propose that CDA1 is a negative regulator of cell growth and that its activity is regulated by its expression level and phosphorylation [10].
• Its open reading frame of 2079 base pairs encodes a predicted polypeptide of 693 amino acids named CDA1 (cell division autoantigen-1) [10].
• Expression of the CDA1 transgene, but not its N terminus, arrests HeLa cell growth, colony numbers, cell density, and bromodeoxyuridine uptake in a dose-dependent manner [10].

Anatomical context of TSPYL2

• Malignant lymphocytes in dermal infiltrates of CTCL tumors showed frequent and intense nuclear staining with anti-PY-STAT3 antibody, indicating a constitutive activation of STAT3 in vivo in tumor stages [11].
• BACKGROUND AND DESIGN--Cutaneous T-cell lymphoma (CTCL) is a slowly advancing disease that initially presents in the skin and may later progress to involve the lymph nodes and viscera [12].
• In the photopheresis apparatus, two synergistic phenomena are initiated: induction of apoptosis of the CTCL cells and mass conversion of blood monocytes to DCs [13].
• Because curative therapies for CTCL are not yet available, short of TSEB in patients who have early-stage disease and allogeneic bone marrow transplantation in patients who have more advanced disease, the goal of current therapies is to prevent progression of MF and to preserve quality of life [14].
• Identification of epitopes for CTCL-specific cytotoxic T lymphocytes [15].

Associations of TSPYL2 with chemical compounds

• CDA1 comprises an N-terminal proline-rich domain, a central basic domain, and a C-terminal bipartite acidic domain [10].
• There is fair evidence for the use of ECP in erythrodermic CTCL and steroid-refractory GVHD, but randomized controlled studies are needed [16].
• Although milestone drugs such as bexarotene have been approved by the FDA- for treatment of CTCL, other agents such as IL-12 may also have a place in treatment of the disease [17].
• The experimental treatment modalities, interferon-alpha and retinoids, especially arotinoid, are most effective in early stages of CTCL; in advanced stages, the effectiveness can be increased by combination regimens [18].
• Hexadecylphosphocholine, a new, well-tolerated topical agent, induced a remission rate of 50%, with 25% complete remission in CTCL patients of stage Ia to IIb [18].

Other interactions of TSPYL2

• The ability of CDA1 to arrest cell growth is abolished by mutation of the two CDK consensus phosphorylation sites [10].

Analytical, diagnostic and therapeutic context of TSPYL2

• Both immunofluorescence and fluorescent protein tagging show that hCINAP is specifically nuclear and distributed in a widespread, diffuse nucleoplasmic pattern, excluding nucleoli, with some concentration also in Cajal bodies [6].
• Immunohistochemistry revealed HLA-G protein expression in 23 (51%) of 45 cases (7 of 10 CBCL, 16 of 35 CTCL) [1].
• Thus, we have defined a "molecular fingerprint" specific for a patient's malignant T-cells and can molecularly diagnose CTCL through PCR amplification [19].
• CTA could provide defined targets for antigen-based vaccination in a high percentage of cases with CTCL [20].
• Here, we studied signal transducers and activators of transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL) [11].

References