Details of Disease

General Information of Disease (ID: DISFMTC7)

• Disease Name: Sezary syndrome
• Synonyms: SS; Sezary's lymphoma; Sezary lymphoma; CTCL / Sezary syndrome; Szary lymphoma; SC)zary syndrome; Sezary's disease; Sezary syndrome; Szary syndrome; cutaneous T-cell lymphoma/Sezary syndrome; Sheehan Syndrome; Sezary disease
• Disease Class: 2B02: Sezary syndrome
• Definition: Sezary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma characterized by a triad of erythroderma, lymphadenopathy and circulating atypical lymphocytes (Sezary cells).
• Disease Hierarchy:
  DISAYSZB: Cutaneous T-cell lymphoma
  DISFMTC7: Sezary syndrome
• ICD Code:
  ICD-11: ICD-11: 2B02
  ICD-10: ICD-10: C84.1
  Expand ICD-11: '2B02
  Expand ICD-10: 'C84.1
• Disease Identifiers:
  MONDO ID: MONDO_0017844
  MESH ID: D012751
  UMLS CUI: C0036920
  MedGen ID: 19959
  Orphanet ID: 3162
  SNOMED CT ID: 118611004

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Mogamulizumab	DMISH0Z	Approved	Monoclonal antibody	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 29 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDKN2A	TTFTWQ8	Limited	Biomarker	[2]
CTLA4	TTI2S1D	Limited	FusionGene	[3]
IL32	TTD4G7L	Limited	Biomarker	[2]
JAK3	TTT7PJU	Limited	Altered Expression	[4]
TNFRSF8	TT2GM5R	Limited	Altered Expression	[5]
BRAF	TT0EOB8	Strong	Biomarker	[6]
BRD9	TTR7L5Y	Strong	Biomarker	[6]
CCR4	TT7HQD0	Strong	Biomarker	[7]
CD28	TTQ13FT	Strong	FusionGene	[3]
CD4	TTN2JFW	Strong	Altered Expression	[8]
CDKN1B	TTLGFVW	Strong	Biomarker	[6]
CREBBP	TTFRCTK	Strong	Biomarker	[6]
DNMT3A	TTJUALD	Strong	Biomarker	[6]
DPP4	TTDIGC1	Strong	Altered Expression	[9]
IL31	TT1RJXK	Strong	Biomarker	[10]
IL7	TT8FRMO	Strong	Biomarker	[11]
KIR2DL1	TT4UXPE	Strong	Altered Expression	[8]
KIR2DL3	TTEX3SI	Strong	Altered Expression	[8]
MAPK1	TT4TQBX	Strong	Biomarker	[6]
PRKG1	TT7IZSA	Strong	Biomarker	[6]
PTPN6	TT369M5	Strong	Altered Expression	[12]
RPS6KA1	TTIXKA4	Strong	Biomarker	[2]
SATB1	TTLFRIC	Strong	Biomarker	[13]
SMARCA4	TTVQEZS	Strong	Biomarker	[6]
TIGIT	TTWNL74	Strong	Biomarker	[14]
TNFRSF1B	TT63WSF	Strong	Biomarker	[15]
TRB	TT84HCW	Strong	Biomarker	[16]
TRBC1	TT1DHW2	Strong	Biomarker	[16]
ZNF217	TTY3BRA	Strong	Altered Expression	[17]

This Disease Is Related to 32 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ARID1A	OTRWDV3P	Limited	Genetic Variation	[18]
HM13	OTGEO1LP	Limited	Biomarker	[19]
NAV3	OT97M1TR	Limited	Genetic Variation	[20]
NKG7	OTXDD006	Limited	Altered Expression	[21]
SDC4	OTKUVUGZ	Limited	Biomarker	[22]
BIN1	OTK8O0X8	Disputed	Altered Expression	[23]
TSPYL2	OTGGW2EF	Disputed	Genetic Variation	[24]
AHI1	OT8K2YWY	Strong	Altered Expression	[25]
CARD11	OTRCTLYC	Strong	Biomarker	[2]
CCR10	OT7ZWSSD	Strong	Biomarker	[26]
CD164	OTZ7FIU8	Strong	Biomarker	[27]
CDO1	OTLG1P77	Strong	Altered Expression	[28]
CHD3	OTDBU4F3	Strong	Biomarker	[6]
CMTM2	OTSJISGF	Strong	Biomarker	[29]
DNM3	OTDMUGCR	Strong	Altered Expression	[28]
FCRL3	OTIFXFWL	Strong	Altered Expression	[14]
HELLS	OTVVV668	Strong	Biomarker	[30]
HHEX	OTLIUVYX	Strong	Biomarker	[30]
IER3	OTZJI5FZ	Strong	Biomarker	[31]
IL2RG	OTRZ3OMY	Strong	Biomarker	[2]
KLHL42	OTK6WARI	Strong	Altered Expression	[28]
KMT2C	OTC59BCO	Strong	Biomarker	[6]
KMT2D	OTTVHCLY	Strong	Biomarker	[6]
MYBL2	OTZ3JX8Q	Strong	Genetic Variation	[17]
MYCL	OT1MFQ5U	Strong	Genetic Variation	[17]
NEDD4L	OT1B19RU	Strong	Altered Expression	[28]
PDCD10	OTCHJTSF	Strong	Altered Expression	[32]
RB1	OT9VMY7B	Strong	Biomarker	[6]
RRBP1	OT4ZTPTM	Strong	Biomarker	[33]
SLFN12	OTTBXM25	Strong	Genetic Variation	[34]
TET2	OTKKT03T	Strong	Biomarker	[6]
TOX	OTE8BL5Z	Strong	Altered Expression	[35]

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] Genomic profiling of Szary syndrome identifies alterations of key T cell signaling and differentiation genes.Nat Genet. 2015 Dec;47(12):1426-34. doi: 10.1038/ng.3444. Epub 2015 Nov 9.
• [3] Genomic analysis of mycosis fungoides and Szary syndrome identifies recurrent alterations in TNFR2.Nat Genet. 2015 Sep;47(9):1056-60. doi: 10.1038/ng.3370. Epub 2015 Aug 10.
• [4] IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF).Cell Cycle. 2014;13(8):1306-12. doi: 10.4161/cc.28256. Epub 2014 Mar 3.
• [5] Primary cutaneous lymphoma in Argentina: a report of a nationwide study of 416 patients.Int J Dermatol. 2019 Apr;58(4):449-455. doi: 10.1111/ijd.14262. Epub 2018 Oct 7.
• [6] The mutational landscape of cutaneous T cell lymphoma and Szary syndrome.Nat Genet. 2015 Dec;47(12):1465-70. doi: 10.1038/ng.3442. Epub 2015 Nov 9.
• [7] Population Pharmacokinetic Modeling of Mogamulizumab in Adults With Cutaneous T-Cell Lymphoma or Adult T-Cell Lymphoma.J Clin Pharmacol. 2020 Jan;60(1):58-66. doi: 10.1002/jcph.1564. Epub 2019 Dec 16.
• [8] Killer cell Ig-like receptors CD158a and CD158b display a coactivatory function, involving the c-Jun NH2-terminal protein kinase signaling pathway, when expressed on malignant CD4+ T cells from a patient with Sezary syndrome.Blood. 2007 Jun 1;109(11):5064-5. doi: 10.1182/blood-2007-02-071993.
• [9] Revisiting the initial diagnosis and blood staging of mycosis fungoides and Szary syndrome with the KIR3DL2 marker.Br J Dermatol. 2020 Jun;182(6):1415-1422. doi: 10.1111/bjd.18481. Epub 2019 Oct 22.
• [10] Analysis of the IL-31 pathway in Mycosis fungoides and Szary syndrome.Arch Dermatol Res. 2015 Aug;307(6):479-85. doi: 10.1007/s00403-014-1527-x. Epub 2014 Dec 7.
• [11] Chronic activation profile of circulating CD8+ T cells in Szary syndrome.Oncotarget. 2017 Dec 16;9(3):3497-3506. doi: 10.18632/oncotarget.23334. eCollection 2018 Jan 9.
• [12] Constitutive activation of STAT3 in Szary syndrome is independent of SHP-1.Leukemia. 2012 Feb;26(2):323-31. doi: 10.1038/leu.2011.198. Epub 2011 Aug 5.
• [13] SNF5 deficiency induces apoptosis resistance by repressing SATB1 expression in Szary syndrome.Leuk Lymphoma. 2018 Oct;59(10):2405-2413. doi: 10.1080/10428194.2017.1422861. Epub 2018 Jan 16.
• [14] Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Szary syndrome.Leuk Lymphoma. 2019 Aug;60(8):1899-1907. doi: 10.1080/10428194.2018.1564827. Epub 2019 Jan 14.
• [15] Targeted killing of TNFR2-expressing tumor cells and T(regs) by TNFR2 antagonistic antibodies in advanced Szary syndrome.Leukemia. 2019 May;33(5):1206-1218. doi: 10.1038/s41375-018-0292-9. Epub 2018 Oct 24.
• [16] A restricted clonal T-cell receptor repertoire in Szary syndrome is indicative of superantigenic stimulation.Br J Dermatol. 2011 Jul;165(1):78-84. doi: 10.1111/j.1365-2133.2011.10308.x. Epub 2011 Jun 2.
• [17] Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas.Blood. 2003 Feb 15;101(4):1513-9. doi: 10.1182/blood-2002-08-2434. Epub 2002 Oct 3.
• [18] Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK-STAT pathway in Szary syndrome.Nat Commun. 2015 Sep 29;6:8470. doi: 10.1038/ncomms9470.
• [19] Expression of cancer/testis antigens in cutaneous T cell lymphomas.Int J Cancer. 2002 Feb 10;97(5):668-70. doi: 10.1002/ijc.1643.
• [20] Primary cutaneous T-cell lymphomas do not show specific NAV3 gene deletion or translocation.J Invest Dermatol. 2008 Oct;128(10):2458-66. doi: 10.1038/jid.2008.113. Epub 2008 May 29.
• [21] Th1 response and cytotoxicity genes are down-regulated in cutaneous T-cell lymphoma.Clin Cancer Res. 2006 Aug 15;12(16):4812-21. doi: 10.1158/1078-0432.CCR-06-0532.
• [22] Szary syndrome cells overexpress syndecan-4 bearing distinct heparan sulfate moieties that suppress T-cell activation by binding DC-HIL and trapping TGF-beta on the cell surface.Blood. 2011 Mar 24;117(12):3382-90. doi: 10.1182/blood-2010-08-302034. Epub 2011 Jan 20.
• [23] BIN1 tumor suppressor regulates Fas/Fas ligand-mediated apoptosis through c-FLIP in cutaneous T-cell lymphoma.Leukemia. 2015 Jun;29(6):1402-13. doi: 10.1038/leu.2015.9. Epub 2015 Jan 12.
• [24] Gene expression profiling and immune cell-type deconvolution highlight robust disease progression and survival markers in multiple cohorts of CTCL patients.Oncoimmunology. 2018 May 31;7(8):e1467856. doi: 10.1080/2162402X.2018.1467856. eCollection 2018.
• [25] Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells.Blood. 2009 May 7;113(19):4646-55. doi: 10.1182/blood-2008-08-174037. Epub 2009 Feb 10.
• [26] Chemokine receptor expression by leukemic T cells of cutaneous T-cell lymphoma: clinical and histopathological correlations.J Invest Dermatol. 2007 Dec;127(12):2882-92. doi: 10.1038/sj.jid.5700916. Epub 2007 Jun 28.
• [27] CD164 identifies CD4(+) T cells highly expressing genes associated with malignancy in Szary syndrome: the Szary signature genes, FCRL3, Tox, and miR-214.Arch Dermatol Res. 2017 Jan;309(1):11-19. doi: 10.1007/s00403-016-1698-8. Epub 2016 Oct 20.
• [28] Szary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3.Leukemia. 2008 Feb;22(2):393-9. doi: 10.1038/sj.leu.2405044. Epub 2007 Nov 22.
• [29] Epigenomic Analysis of Szary Syndrome Defines Patterns of Aberrant DNA Methylation and Identifies DiagnosticMarkers.J Invest Dermatol. 2016 Sep;136(9):1876-1884. doi: 10.1016/j.jid.2016.03.042. Epub 2016 Apr 23.
• [30] Fine mapping of chromosome 10q deletions in mycosis fungoides and sezary syndrome: identification of two discrete regions of deletion at 10q23.33-24.1 and 10q24.33-25.1.Genes Chromosomes Cancer. 2005 Feb;42(2):184-92. doi: 10.1002/gcc.20115.
• [31] Resistance of Szary cells to TNF--induced apoptosis is mediated in part by a loss of TNFR1 and a high level of the IER3 expression.Exp Dermatol. 2012 Apr;21(4):287-92. doi: 10.1111/j.1600-0625.2012.01452.x.
• [32] Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis.APMIS. 2010 Oct;118(10):719-28. doi: 10.1111/j.1600-0463.2010.02669.x. Epub 2010 Aug 19.
• [33] Transcriptome analysis of Szary syndrome and lymphocytic-variant hypereosinophilic syndrome T cells reveals common and divergent genes.Oncotarget. 2019 Aug 20;10(49):5052-5069. doi: 10.18632/oncotarget.27120. eCollection 2019 Aug 20.
• [34] Novel TBL1XR1, EPHA7 and SLFN12 mutations in a Sezary syndrome patient discovered by whole exome sequencing.Exp Dermatol. 2014 May;23(5):366-8. doi: 10.1111/exd.12405.
• [35] Molecular profiling of TOX-deficient neoplastic cells in cutaneous T cell lymphoma.Arch Dermatol Res. 2020 Sep;312(7):513-525. doi: 10.1007/s00403-019-02000-0. Epub 2019 Nov 1.