Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVN0MNW)

• DOT Name: T-cell leukemia homeobox protein 1 (TLX1)
• Synonyms: Homeobox protein Hox-11; Proto-oncogene TCL-3; T-cell leukemia/lymphoma protein 3
• Gene Name: TLX1
• Related Disease:
  Advanced cancer
  T-lymphoblastic lymphoma
  Acute lymphocytic leukaemia
  Adult T-cell leukemia/lymphoma
  Autoimmune disease
  B-cell lymphoma
  B-cell neoplasm
  Central hypoventilation syndrome, congenital
  Childhood acute lymphoblastic leukemia
  Chromosomal disorder
  leukaemia
  Lymphoblastic lymphoma
  Lymphoma
  Neoplasm
  Precancerous condition
  Splenic disorder
  46,XY disorder of sex development
  Adult lymphoma
  Brain neoplasm
  Hereditary breast carcinoma
  Neuroblastoma
  Pediatric lymphoma
  Primitive neuroectodermal tumor
  Gastric cancer
  Leukemia
  Lymphoid leukemia
  Stomach cancer
• UniProt ID: TLX1_HUMAN
• Pfam ID: PF00046
• Sequence:
  MEHLGPHHLHPGHAEPISFGIDQILNSPDQGGCMGPASRLQDGEYGLGCLVGGAYTYGGG
  GSAAATGAGGAGAYGTGGPGGPGGPAGGGGACSMGPLTGSYNVNMALAGGPGPGGGGGSS
  GGAGALSAAGVIRVPAHRPLAGAVAHPQPLATGLPTVPSVPAMPGVNNLTGLTFPWMESN
  RRYTKDRFTGHPYQNRTPPKKKKPRTSFTRLQICELEKRFHRQKYLASAERAALAKALKM
  TDAQVKTWFQNRRTKWRRQTAEEREAERQQANRILLQLQQEAFQKSLAQPLPADPLCVHN
  SSLFALQNLQPWSDDSTKITSVTSVASACE
• Function: Controls the genesis of the spleen. Binds to the DNA sequence 5'-GGCGGTAAGTGG-3'.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
T-lymphoblastic lymphoma	DISGFZXW	Definitive	Altered Expression	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[3]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[4]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[1]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[6]
Central hypoventilation syndrome, congenital	DISQRK53	Strong	Biomarker	[7]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[3]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[8]
leukaemia	DISS7D1V	Strong	Biomarker	[9]
Lymphoblastic lymphoma	DISB9ZYC	Strong	Biomarker	[10]
Lymphoma	DISN6V4S	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Precancerous condition	DISV06FL	Strong	Biomarker	[12]
Splenic disorder	DISCUUIU	Strong	Biomarker	[13]
46,XY disorder of sex development	DIS78CGG	moderate	Genetic Variation	[14]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[11]
Brain neoplasm	DISY3EKS	moderate	Biomarker	[15]
Hereditary breast carcinoma	DISAEZT5	moderate	Biomarker	[16]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[15]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[11]
Primitive neuroectodermal tumor	DISFHXHA	moderate	Altered Expression	[15]
Gastric cancer	DISXGOUK	Limited	Biomarker	[17]
Leukemia	DISNAKFL	Limited	Biomarker	[9]
Lymphoid leukemia	DIS65TYQ	Limited	Genetic Variation	[8]
Stomach cancer	DISKIJSX	Limited	Biomarker	[17]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of T-cell leukemia homeobox protein 1 (TLX1).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of T-cell leukemia homeobox protein 1 (TLX1).	[19]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of T-cell leukemia homeobox protein 1 (TLX1).	[20]

References

• [1] Loss of Ubr1 promotes aneuploidy and accelerates B-cell lymphomagenesis in TLX1/HOX11-transgenic mice.Oncogene. 2006 Sep 21;25(42):5752-63. doi: 10.1038/sj.onc.1209573. Epub 2006 Jul 24.
• [2] T cell receptor genotyping and HOXA/TLX1 expression define three T lymphoblastic lymphoma subsets which might affect clinical outcome.Clin Cancer Res. 2008 Feb 1;14(3):692-700. doi: 10.1158/1078-0432.CCR-07-1927.
• [3] Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid leukemias and affect microRNA binding.J Hematol Oncol. 2014 Jun 2;7:43. doi: 10.1186/1756-8722-7-43.
• [4] Overexpression of stem cell associated ALDH1A1, a target of the leukemogenic transcription factor TLX1/HOX11, inhibits lymphopoiesis and promotes myelopoiesis in murine hematopoietic progenitors.Leuk Res. 2008 Jun;32(6):873-83. doi: 10.1016/j.leukres.2007.11.001. Epub 2007 Dec 21.
• [5] Fetal Hox11 expression patterns predict defective target organs: a novel link between developmental biology and autoimmunity.Immunol Cell Biol. 2008 May-Jun;86(4):301-9. doi: 10.1038/icb.2008.6. Epub 2008 Feb 26.
• [6] Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice.Oncogene. 2006 Apr 27;25(18):2575-87. doi: 10.1038/sj.onc.1209285.
• [7] Mutational analysis of the RNX gene in congenital central hypoventilation syndrome.Am J Med Genet. 2002 Nov 22;113(2):178-82. doi: 10.1002/ajmg.10746.
• [8] Simultaneous translocation of both TCR Loci (14q11) with rare partner loci (Xq22 and 12p13) in a case of T-lymphoblastic leukemia.Ann Lab Med. 2012 May;32(3):220-4. doi: 10.3343/alm.2012.32.3.220. Epub 2012 Apr 18.
• [9] Characterization of the genome-wide TLX1 binding profile in T-cell acute lymphoblastic leukemia.Leukemia. 2015 Dec;29(12):2317-27. doi: 10.1038/leu.2015.162. Epub 2015 Jun 25.
• [10] A novel translocation, t(9;17)(q34;q23), in aggressive childhood lymphoblastic lymphoma.Leukemia. 1988 Nov;2(11):745-8.
• [11] Transient responses to NOTCH and TLX1/HOX11 inhibition in T-cell acute lymphoblastic leukemia/lymphoma.PLoS One. 2011 Feb 4;6(2):e16761. doi: 10.1371/journal.pone.0016761.
• [12] Induction of tolerance to immunogenic tumor antigens associated with lymphomagenesis in HOX11 transgenic mice.Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13300-5. doi: 10.1073/pnas.240221297.
• [13] Hox11 controls the genesis of the spleen.Nature. 1994 Apr 21;368(6473):747-9. doi: 10.1038/368747a0.
• [14] Testicular differentiation factor SF-1 is required for human spleen development.J Clin Invest. 2014 May;124(5):2071-5. doi: 10.1172/JCI73186. Epub 2014 Apr 8.
• [15] Specific alternative HOX11 transcripts are expressed in paediatric neural tumours and T-cell acute lymphoblastic leukaemia.Gene. 2003 Dec 24;323:89-99. doi: 10.1016/j.gene.2003.09.001.
• [16] HOX gene methylation status analysis in patients with hereditary breast cancer.J Hum Genet. 2013 Jan;58(1):51-3. doi: 10.1038/jhg.2012.118. Epub 2012 Oct 11.
• [17] Gene regulatory network construction identified NFYA as a diffuse subtype-specific prognostic factor in gastric cancer.Int J Oncol. 2018 Nov;53(5):1857-1868. doi: 10.3892/ijo.2018.4519. Epub 2018 Aug 9.
• [18] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [19] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [20] 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.