Details of Disease

General Information of Disease (ID: DISHOPPI)

• Disease Name: Large granular lymphocytic leukemia
• Synonyms: LGL leukemia; large granular lymphocyte leukaemia; TLGL; large granular lymphocyte leukemia; LGL leukaemia; T-gamma lymphoproliferative disorder; T-LGL leukaemia; T-cell large granular lymphocytic leukaemia; large cell granular lymphogenous leukemia; LGLL; large cell granular lymphogenous leukaemia; T-cell large granular lymphocyte leukemia; Tgamma large granular lymphocyte leukaemia; T-cell LGL leukaemia; large granular lymphocytic leukaemia; T-cell LGL leukemia; T gamma lymphoproliferative disorder; T-cell large gran. lymph. leuk.; T-LGL leukemia; leukemia, large granular LYMPHOCYTIC, malignant; T-cell large granular lymphocytic leukemia; large granular lymphocytic leukemia; proliferation of large granular lymphocytes; large cell granular lymphoid leukaemia; T-LGL; Tgamma large granular lymphocyte leukemia; large cell granular lymphoid leukemia; large granular lymphocytosis
• Disease Class: 2A90: Mature T-cell lymphoma
• Definition: T-cell large granular lymphocyte leukemia (T-cell LGL leukemia) is a lymphoproliferative malignancy that arises from the mature T-cell (CD3+) lineage.
• Disease Hierarchy:
  DIS0C4XI: Chronic leukemia
  DIS65TYQ: Lymphoid leukemia
  DISCDT4E: Peripheral T-cell lymphoma
  DISAEGPH: Immune system disorder
  DISHOPPI: Large granular lymphocytic leukemia
• ICD Code: ICD-11: ICD-11: 2A90.1
• Disease Identifiers:
  MONDO ID: MONDO_0019469
  MESH ID: D054066
  UMLS CUI: C1955861
  MedGen ID: 363038
  Orphanet ID: 86872
  SNOMED CT ID: 128819001

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 9 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Fludarabine	DMVRLT7	Approved	Small molecular drug	[1]
Lenalidomide	DM6Q7U4	Approved	Small molecular drug	[2]
Mycophenolate mofetil	DMPQAGE	Approved	Small molecular drug	[3]
Mycophenolic acid	DMRBMAU	Approved	NA	[4]
Rituximab	DM1YVZT	Approved	Antibody	[5]
Sunitinib	DMCBJSR	Approved	Small molecular drug	[6]
Tacrolimus	DMZ7XNQ	Approved	Small molecular drug	[7]
Thalidomide	DM70BU5	Approved	Small molecular drug	[8]
Vidarabine	DM0N85H	Approved	Small molecular drug	[9]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
BNZ-1	DM8JQZC	Phase 2	Peptide	[10]

This Disease is Treated as An Indication in 1 Drugs in Phase 2 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
Cyclosporin A	DMUYKBZ	Phase 2 Trial	Small molecular drug	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
NCAM1	TTVXPHT	Limited	Biomarker	[11]
IL15	TTJFA35	Strong	Biomarker	[12]
IL15RA	TTGN89I	Strong	Altered Expression	[13]
STAT3	TTHJT3X	Strong	Genetic Variation	[14]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
B3GAT1	OTXFP98E	Strong	Biomarker	[15]
PKHD1L1	OTREFCAA	Strong	Biomarker	[16]
RAB4A	OT7BL9WW	Strong	Genetic Variation	[17]
SBF1	OTW6I9RV	Strong	Biomarker	[16]
STAT5B	OTZVPEBT	Strong	Biomarker	[18]

References

• [1] Fludarabine FDA Label
• [2] Lenalidomide FDA Label
• [3] Mycophenolate mofetil FDA Label
• [4] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [5] Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series. Semin Arthritis Rheum. 2020 Oct;50(5):1109-1113.
• [6] Sunitinib FDA Label
• [7] Tacrolimus FDA Label
• [8] Thalidomide FDA Label
• [9] Vidarabine FDA Label
• [10] ClinicalTrials.gov (NCT03239392) A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL. U.S. National Institutes of Health.
• [11] Atypical Presentation of T-Cell Large Granular Lymphocytic Leukemia Mimicking Pleural Malignancy on 18F-FDG PET/CT.Clin Nucl Med. 2019 Apr;44(4):e296-e297. doi: 10.1097/RLU.0000000000002425.
• [12] IL-2 and IL-15 blockade by BNZ-1, an inhibitor of selective -chain cytokines, decreases leukemic T-cell viability.Leukemia. 2019 May;33(5):1243-1255. doi: 10.1038/s41375-018-0290-y. Epub 2018 Oct 23.
• [13] Increased serum soluble IL-15R levels in T-cell large granular lymphocyte leukemia.Blood. 2012 Jan 5;119(1):137-43. doi: 10.1182/blood-2011-04-346759. Epub 2011 Nov 2.
• [14] Stat3 mutations impact on overall survival in large granular lymphocyte leukemia: a single-center experience of 205 patients.Leukemia. 2020 Apr;34(4):1116-1124. doi: 10.1038/s41375-019-0644-0. Epub 2019 Nov 18.
• [15] Refining the diagnosis of T-cell large granular lymphocytic leukemia by combining distinct patterns of antigen expression with T-cell clonality studies.Leukemia. 2011 Sep;25(9):1439-43. doi: 10.1038/leu.2011.107. Epub 2011 May 27.
• [16] Submicroscopic genomic rearrangements change gene expression in T-cell large granular lymphocyte leukemia.Eur J Haematol. 2014 Aug;93(2):143-9. doi: 10.1111/ejh.12318. Epub 2014 Apr 9.
• [17] Increased seroreactivity to human T cell lymphoma/leukemia virus-related endogenous sequence-1 Gag peptides in patients with human T cell lymphoma/leukemia virus myelopathy.AIDS Res Hum Retroviruses. 2015 Feb;31(2):242-9. doi: 10.1089/AID.2014.0171. Epub 2014 Nov 19.
• [18] Mutations in the signal transducer and activator of transcription family of genes in cancer.Cancer Sci. 2018 Apr;109(4):926-933. doi: 10.1111/cas.13525. Epub 2018 Mar 2.