Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4CSO39)

DOT Name T-cell leukemia/lymphoma protein 1B (TCL1B)
Synonyms Oncogene TCL-1B; Oncogene TCL1B; SYN-1; Syncytiotrophoblast-specific protein; TCL1/MTCP1-like protein 1
Gene Name TCL1B
Related Disease
Acute myelogenous leukaemia ( )
Central nervous system neoplasm ( )
T-cell acute lymphoblastic leukaemia ( )
Acute lymphocytic leukaemia ( )
Adult lymphoma ( )
AIDS-related lymphoma ( )
Alzheimer disease ( )
Anemia ( )
B-cell acute lymphoblastic leukaemia ( )
B-cell neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Burkitt lymphoma ( )
Childhood acute lymphoblastic leukemia ( )
Chromosomal disorder ( )
Epstein barr virus infection ( )
Fibrosarcoma ( )
Follicular lymphoma ( )
Haematological malignancy ( )
Hepatocellular carcinoma ( )
Immunodeficiency ( )
Lymphoma ( )
Lymphoma, non-Hodgkin, familial ( )
Malignant peripheral nerve sheath tumor ( )
Malignant soft tissue neoplasm ( )
Mantle cell lymphoma ( )
Mycosis fungoides ( )
Non-hodgkin lymphoma ( )
Pediatric lymphoma ( )
Primary cutaneous peripheral T-cell lymphoma not otherwise specified ( )
Richter syndrome ( )
Sarcoidosis ( )
Sarcoma ( )
T-cell leukaemia ( )
T-cell lymphoma ( )
Alopecia ( )
Lymphoproliferative syndrome ( )
MALT lymphoma ( )
Melanoma ( )
Parkinson disease ( )
Adult T-cell leukemia/lymphoma ( )
leukaemia ( )
Leukemia ( )
Plasma cell myeloma ( )
Prolymphocytic leukaemia ( )
Waldenstrom macroglobulinemia ( )
UniProt ID
TCL1B_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF01840
Sequence
MASEASVRLGVPPGRLWIQRPGIYEDEEGRTWVTVVVRFNPSRREWARASQGSRYEPSIT
VHLWQMAVHTRELLSSGQMPFSQLPAVWQLYPGRKYRAADSSFWEIADHGQIDSMEQLVL
TYQPERKD
Function Enhances the phosphorylation and activation of AKT1 and AKT2.
Tissue Specificity Expressed in a variety of tissues including placenta and testis.
KEGG Pathway
PI3K-Akt sig.ling pathway (hsa04151 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Definitive Genetic Variation [1]
Central nervous system neoplasm DISFC18W Definitive Biomarker [2]
T-cell acute lymphoblastic leukaemia DIS17AI2 Definitive Genetic Variation [3]
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [4]
Adult lymphoma DISK8IZR Strong Biomarker [5]
AIDS-related lymphoma DISSLRAU Strong Biomarker [6]
Alzheimer disease DISF8S70 Strong Biomarker [7]
Anemia DISTVL0C Strong Altered Expression [8]
B-cell acute lymphoblastic leukaemia DISKLOKC Strong Altered Expression [9]
B-cell neoplasm DISVY326 Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Genetic Variation [10]
Breast carcinoma DIS2UE88 Strong Genetic Variation [10]
Breast neoplasm DISNGJLM Strong Biomarker [11]
Burkitt lymphoma DIS9D5XU Strong Altered Expression [12]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Genetic Variation [4]
Chromosomal disorder DISM5BB5 Strong Genetic Variation [13]
Epstein barr virus infection DISOO0WT Strong Altered Expression [14]
Fibrosarcoma DISWX7MU Strong Biomarker [15]
Follicular lymphoma DISVEUR6 Strong Altered Expression [16]
Haematological malignancy DISCDP7W Strong Altered Expression [17]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [18]
Immunodeficiency DIS093I0 Strong Genetic Variation [19]
Lymphoma DISN6V4S Strong Biomarker [5]
Lymphoma, non-Hodgkin, familial DISCXYIZ Strong Biomarker [20]
Malignant peripheral nerve sheath tumor DIS0JTN6 Strong Biomarker [15]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [15]
Mantle cell lymphoma DISFREOV Strong Altered Expression [8]
Mycosis fungoides DIS62RB8 Strong Altered Expression [21]
Non-hodgkin lymphoma DISS2Y8A Strong Biomarker [20]
Pediatric lymphoma DIS51BK2 Strong Biomarker [5]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified DIS5OHQF Strong Genetic Variation [22]
Richter syndrome DISBX2TK Strong Biomarker [23]
Sarcoidosis DISE5B8Z Strong Altered Expression [24]
Sarcoma DISZDG3U Strong Biomarker [15]
T-cell leukaemia DISJ6YIF Strong Biomarker [25]
T-cell lymphoma DISSXRTQ Strong Altered Expression [21]
Alopecia DIS37HU4 moderate Biomarker [26]
Lymphoproliferative syndrome DISMVL8O moderate Biomarker [27]
MALT lymphoma DIS1AVVE moderate Altered Expression [28]
Melanoma DIS1RRCY moderate Altered Expression [29]
Parkinson disease DISQVHKL moderate Biomarker [30]
Adult T-cell leukemia/lymphoma DIS882XU Disputed Biomarker [31]
leukaemia DISS7D1V Limited Genetic Variation [32]
Leukemia DISNAKFL Limited Genetic Variation [32]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [6]
Prolymphocytic leukaemia DISDPPHX Limited Genetic Variation [22]
Waldenstrom macroglobulinemia DIS9O23I Limited Genetic Variation [33]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of T-cell leukemia/lymphoma protein 1B (TCL1B). [34]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of T-cell leukemia/lymphoma protein 1B (TCL1B). [35]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of T-cell leukemia/lymphoma protein 1B (TCL1B). [36]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of T-cell leukemia/lymphoma protein 1B (TCL1B). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of T-cell leukemia/lymphoma protein 1B (TCL1B). [38]
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References

1 TET2 mutations, myelodysplastic features, and a distinct immunoprofile characterize blastic plasmacytoid dendritic cell neoplasm in the bone marrow.Am J Hematol. 2013 Dec;88(12):1055-61. doi: 10.1002/ajh.23567. Epub 2013 Sep 30.
2 Transcriptional profiling of medulloblastoma with extensive nodularity (MBEN) reveals two clinically relevant tumor subsets with VSNL1 as potent prognostic marker.Acta Neuropathol. 2020 Mar;139(3):583-596. doi: 10.1007/s00401-019-02102-z. Epub 2019 Nov 28.
3 Tcr translocations that delete the Bcl11b haploinsufficient tumor suppressor gene promote atm-deficient T cell acute lymphoblastic leukemia.Cell Cycle. 2014;13(19):3076-82. doi: 10.4161/15384101.2014.949144.
4 IGH gene involvement in two cases of acute lymphoblastic leukemia with t(14;14)(q11;q32) identified by sequential R-banding and fluorescence in situ hybridization.Cancer Genet Cytogenet. 2004 Jul 15;152(2):141-5. doi: 10.1016/j.cancergencyto.2003.11.008.
5 The NF-B subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma.Oncogene. 2016 Jun 30;35(26):3476-84. doi: 10.1038/onc.2015.399. Epub 2015 Nov 2.
6 TCL1 oncogene expression in B cell subsets from lymphoid hyperplasia and distinct classes of B cell lymphoma.Lab Invest. 2001 Apr;81(4):555-64. doi: 10.1038/labinvest.3780264.
7 Characterization of the precursor protein of the non-A beta component of senile plaques (NACP) in the human central nervous system.J Neuropathol Exp Neurol. 1996 Aug;55(8):889-95. doi: 10.1097/00005072-199608000-00004.
8 TCL1 expression predicts overall survival in patients with mantle cell lymphoma.Eur J Haematol. 2015 Dec;95(6):583-94. doi: 10.1111/ejh.12539. Epub 2015 Mar 16.
9 Differential expression of TCL1 during pre-B-cell acute lymphoblastic leukemia progression.Cancer Genet Cytogenet. 2002 Jun;135(2):110-9. doi: 10.1016/s0165-4608(01)00655-0.
10 Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth.Nat Med. 2017 Jan;23(1):120-127. doi: 10.1038/nm.4232. Epub 2016 Nov 21.
11 Subcellular localization of activated AKT in estrogen receptor- and progesterone receptor-expressing breast cancers: potential clinical implications.Am J Pathol. 2010 May;176(5):2139-49. doi: 10.2353/ajpath.2010.090477. Epub 2010 Mar 12.
12 MiR-29 silencing modulates the expression of target genes related to proliferation, apoptosis and methylation in Burkitt lymphoma cells.J Cancer Res Clin Oncol. 2018 Mar;144(3):483-497. doi: 10.1007/s00432-017-2575-3. Epub 2018 Jan 9.
13 Prognostic significance of cytogenetic abnormalities in T-cell prolymphocytic leukemia.Am J Hematol. 2017 May;92(5):441-447. doi: 10.1002/ajh.24679. Epub 2017 Feb 27.
14 TCL1 expression and Epstein-Barr virus status in pediatric Burkitt lymphoma.Am J Clin Pathol. 2005 Oct;124(4):569-75. doi: 10.1309/77V7U4E03V69QHRR.
15 Purification and characterization of human lung fibroblast motility-stimulating factor for human soft tissue sarcoma cells: identification as an NH2-terminal fragment of human fibronectin.Cancer Res. 1997 Aug 15;57(16):3577-84.
16 TCL1: a shared tumor-associated antigen for immunotherapy against B-cell lymphomas.Blood. 2012 Aug 23;120(8):1613-23. doi: 10.1182/blood-2011-09-382838. Epub 2012 May 29.
17 Expression of the TCL1 gene at 14q32 in B-cell malignancies but not in adult T-cell leukemia.Jpn J Cancer Res. 1998 Jul;89(7):712-8. doi: 10.1111/j.1349-7006.1998.tb03275.x.
18 PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis.Gut. 2014 Oct;63(10):1635-47. doi: 10.1136/gutjnl-2013-305302. Epub 2013 Dec 18.
19 Chromosome walking on the TCL1 locus involved in T-cell neoplasia.Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9275-9. doi: 10.1073/pnas.90.20.9275.
20 EBNA2 interferes with the germinal center phenotype by downregulating BCL6 and TCL1 in non-Hodgkin's lymphoma cells.J Virol. 2007 Mar;81(5):2274-82. doi: 10.1128/JVI.01822-06. Epub 2006 Dec 6.
21 Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues.Cancer Res. 2000 Apr 15;60(8):2095-100.
22 Incidence of TCR and TCL1 gene translocations and isochromosome 7q in peripheral T-cell lymphomas using fluorescence in situ hybridization.Am J Clin Pathol. 2008 Aug;130(2):178-85. doi: 10.1309/PNXUKA1CFJMVGCN1.
23 Loss of NFAT2 expression results in the acceleration of clonal evolution in chronic lymphocytic leukemia.J Leukoc Biol. 2019 Mar;105(3):531-538. doi: 10.1002/JLB.2AB0218-076RR. Epub 2018 Dec 17.
24 Expression of sarcoidosis related genes in lung lavage cells.Sarcoidosis Vasc Diffuse Lung Dis. 2002 Mar;19(1):59-65.
25 T-Cell Leukemia/Lymphoma 1 (TCL1): An Oncogene Regulating Multiple Signaling Pathways.Front Oncol. 2018 Aug 13;8:317. doi: 10.3389/fonc.2018.00317. eCollection 2018.
26 T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1.PLoS One. 2018 Oct 4;13(10):e0204775. doi: 10.1371/journal.pone.0204775. eCollection 2018.
27 Effect of rapamycin on mouse chronic lymphocytic leukemia and the development of nonhematopoietic malignancies in Emu-TCL1 transgenic mice.Cancer Res. 2006 Jan 15;66(2):915-20. doi: 10.1158/0008-5472.CAN-05-3426.
28 Activation of the TCL1 protein in B cell lymphomas.Pathol Int. 2000 Mar;50(3):191-9. doi: 10.1046/j.1440-1827.2000.01023.x.
29 MicroRNA-143 targets Syndecan-1 to repress cell growth in melanoma.PLoS One. 2014 Apr 10;9(4):e94855. doi: 10.1371/journal.pone.0094855. eCollection 2014.
30 Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls.Neurobiol Aging. 2015 Feb;36(2):1105-9. doi: 10.1016/j.neurobiolaging.2014.10.039. Epub 2014 Nov 5.
31 The role of TCL1 in human T-cell leukemia.Oncogene. 2001 Sep 10;20(40):5638-43. doi: 10.1038/sj.onc.1204596.
32 PI3K p110 inactivation antagonizes chronic lymphocytic leukemia and reverses T cell immune suppression.J Clin Invest. 2019 Jan 2;129(1):122-136. doi: 10.1172/JCI99386. Epub 2018 Nov 19.
33 Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrm macroglobulinemia.Nat Commun. 2018 Oct 10;9(1):4182. doi: 10.1038/s41467-018-06541-2.
34 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
35 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
36 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
37 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
38 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.