Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCNOV1M)

• DOT Name: Protein lyl-1 (LYL1)
• Synonyms: Class A basic helix-loop-helix protein 18; bHLHa18; Lymphoblastic leukemia-derived sequence 1
• Gene Name: LYL1
• Related Disease:
  Adult lymphoma
  B-cell neoplasm
  Lymphoma
  Pediatric lymphoma
  Acute erythroid leukemia
  Acute leukaemia
  Acute myelogenous leukaemia
  Acute undifferentiated leukemia
  Advanced cancer
  Childhood myelodysplastic syndrome
  Chromosomal disorder
  Endometrial carcinoma
  Lymphoid leukemia
  Myelodysplastic syndrome
  T-cell acute lymphoblastic leukaemia
  Acute lymphocytic leukaemia
  T-cell leukaemia
• UniProt ID: LYL1_HUMAN
• Pfam ID: PF00010
• Sequence:
  MCPPQAQAEVGPTMTEKAEMVCAPSPAPAPPPKPASPGPPQVEEVGHRGGSSPPRLPPGV
  PVISLGHSRPPGVAMPTTELGTLRPPLLQLSTLGTAPPTLALHYHPHPFLNSVYIGPAGP
  FSIFPSSRLKRRPSHCELDLAEGHQPQKVARRVFTNSRERWRQQNVNGAFAELRKLLPTH
  PPDRKLSKNEVLRLAMKYIGFLVRLLRDQAAALAAGPTPPGPRKRPVHRVPDDGARRGSG
  RRAEAAARSQPAPPADPDGSPGGAARPIKMEQTALSPEVR
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway: NGF-stimulated transcription (R-HSA-9031628)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Definitive	Biomarker	[1]
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Lymphoma	DISN6V4S	Definitive	Biomarker	[1]
Pediatric lymphoma	DIS51BK2	Definitive	Biomarker	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Biomarker	[2]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Altered Expression	[7]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[8]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[6]
Lymphoid leukemia	DIS65TYQ	Strong	Genetic Variation	[9]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[7]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[4]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Genetic Variation	[9]
T-cell leukaemia	DISJ6YIF	Limited	Altered Expression	[10]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cytarabine	DMZD5QR	Approved	Protein lyl-1 (LYL1) decreases the response to substance of Cytarabine.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein lyl-1 (LYL1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein lyl-1 (LYL1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein lyl-1 (LYL1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein lyl-1 (LYL1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein lyl-1 (LYL1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein lyl-1 (LYL1).	[16]

References

• [1] Overexpression of a transcription factor LYL1 induces T- and B-cell lymphoma in mice.Oncogene. 2007 Oct 18;26(48):6937-47. doi: 10.1038/sj.onc.1210494. Epub 2007 May 7.
• [2] A novel role for Lyl1 in primitive erythropoiesis.Development. 2018 Oct 11;145(19):dev162990. doi: 10.1242/dev.162990.
• [3] TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia.Semin Cancer Biol. 1993 Dec;4(6):341-7.
• [4] The NUP98-HOXD13 fusion oncogene induces thymocyte self-renewal via Lmo2/Lyl1.Leukemia. 2019 Aug;33(8):1868-1880. doi: 10.1038/s41375-018-0361-0. Epub 2019 Jan 30.
• [5] Concise review: Blood relatives: formation and regulation of hematopoietic stem cells by the basic helix-loop-helix transcription factors stem cell leukemia and lymphoblastic leukemia-derived sequence 1.Stem Cells. 2012 Jun;30(6):1053-8. doi: 10.1002/stem.1093.
• [6] LYL1 gene amplification predicts poor survival of patients with uterine corpus endometrial carcinoma: analysis of the Cancer genome atlas data.BMC Cancer. 2018 May 2;18(1):494. doi: 10.1186/s12885-018-4429-z.
• [7] Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia. Leukemia. 2005 Nov;19(11):1941-7. doi: 10.1038/sj.leu.2403836.
• [8] Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements.Haematologica. 2012 Feb;97(2):258-61. doi: 10.3324/haematol.2011.051722. Epub 2011 Nov 4.
• [9] Shared roles for Scl and Lyl1 in murine platelet production and function.Blood. 2019 Sep 5;134(10):826-835. doi: 10.1182/blood.2019896175. Epub 2019 Jul 12.
• [10] Requirement for Lyl1 in a model of Lmo2-driven early T-cell precursor ALL.Blood. 2013 Sep 19;122(12):2093-103. doi: 10.1182/blood-2012-09-458570. Epub 2013 Aug 7.
• [11] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [12] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [13] 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.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [17] Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia. Leukemia. 2005 Nov;19(11):1941-7. doi: 10.1038/sj.leu.2403836.