TMEM244 Gene Expression as a Potential Blood Diagnostic Marker Distinguishing Sézary Syndrome from Mycosis Fungoides and Benign Erythroderma

Sézary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL). The disease is characterized by severe erythroderma, generalized lymphadenopathy, and the presence of circulating Sézary cells that are a clonal proliferation of CD4+/CD45RO+ malignant T lymphocytes primarily involving the skin ( Huet et al., 2006 Huet D. Bagot M. Loyaux D. Capdevielle J. Conraux L. Ferrara P. et al. SC5 mAb represents a unique tool for the detection of extracellular vimentin as a specific marker of Sezary cells. J Immunol. 2006; 176: 652-659 Crossref PubMed Scopus (59) Google Scholar ; Willemze et al., 2005 Willemze R. Jaffe E.S. Burg G. Cerroni L. Berti E. Swerdlow S.H. et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005; 105: 3768-3785 Crossref PubMed Scopus (3293) Google Scholar ). SS is a leukemic variant of CTCL and is closely related to mycosis fungoides (MF), a more indolent and slowly progressing type ( Booken et al., 2008 Booken N. Gratchev A. Utikal J. Weiss C. Yu X. Qadoumi M. et al. Sezary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3. Leukemia. 2008; 22: 393-399 Crossref PubMed Scopus (83) Google Scholar ). MF is the most common type of CTCL (50‒70%), whereas patients with SS represent approximately 5% of CTCL cases. The incidence rate of CTCL is increasing and is currently 0.77 of 100,000 ( Bradford et al., 2009 Bradford P.T. Devesa S.S. Anderson W.F. Toro J.R. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009; 113: 5064-5073 Crossref PubMed Scopus (518) Google Scholar ; Criscione and Weinstock, 2007 Criscione V.D. Weinstock M.A. Incidence of cutaneous T-cell lymphoma in the United States, 1973–2002. Arch Dermatol. 2007; 143: 854-859 Crossref PubMed Scopus (408) Google Scholar ). The International Society of Cutaneous Lymphomas‒proposed criteria for SS diagnosis integrate clinical, immunophenotyping, histopathologic, and molecular studies ( Hristov et al., 2019 Hristov A.C. Tejasvi T. Wilcox R.A. Mycosis fungoides and Sezary syndrome: 2019 update on diagnosis, risk-stratification, and management. Am J Hematol. 2019; 94: 1027-1041 Crossref PubMed Scopus (58) Google Scholar ). However, owing to great molecular heterogeneity between individual patients and the fact that SS can mimic many common benign chronic dermatoses such as psoriasis, pityriasis rubra pilaris, dermatitis, etc. as well as MF, the correct diagnosis is often very challenging ( Vakiti et al., 2022 Vakiti A. Padala S.A. Singh D. Sezary syndrome. Treasure Island. StatPearls, FL2022 Google Scholar ). Moreover, the lack of correct diagnostic tools often leads to delays in diagnosis and inappropriate treatment that adversely affect the outcome of this aggressive disease. Despite advances in therapy, the prognosis still remains poor, with a 5-year overall survival of 30% ( Najidh et al., 2021 Najidh S. Tensen C.P. van der Sluijs-Gelling A.J. Teodosio C. Cats D. Mei H. et al. Improved Sezary cell detection and novel insights into immunophenotypic and molecular heterogeneity in Sezary syndrome. Blood. 2021; 138: 2539-2554 Crossref PubMed Scopus (19) Google Scholar ).