| Note | |
| | |
| Entity | t(7;19)(q35;p13) --> TCRB/LYL1 in T-cell acute lymphoblastic leukemia, other T-ALL, acute myeloblastic leukemia (AML) or myelodysplastic syndrome (MDS) |
| Disease | The LYL1 gene was originally identified at the chromosomal translocation t(7;19)(q35;p13) associated with T-ALL. However, over-expression of LYL1 has been reported in T-ALL cases without apparent chromosome aberration. Recent studies on leukemia cell lines and patient samples suggested its involvement in myeloid malignancies. Using real-time quantitative RT-PCR assay, the authors found that the expression of LYL1 was at a significantly higher level than normal bone marrow cells in the majority of cases of acute myeloblastic leukemia (AML) or myelodysplastic syndrome when compared to normal bone marrow. This study also showed that LYL1 was highly expressed in most AML cell lines and in CD34(+) AML cells. |
| Prognosis | Expression of LYL1 is associated with unfavorable prognosis in T-ALL cases. LYL1(+) cases have a gene expression signature corresponding to that of the most immature normal T-cell precursors (CD4/CD8 double-negative cells), which express CD34 but not CD4, CD8, or CD3. Less favorable outcomes were observed in subgroups defined by gene expression profiles characteristic of TAL1(+) or LYL1(+) samples, which resemble late cortical and early pro-T thymocytes, respectively. |
| Cytogenetics | The LYL1 gene was originally identified at the breakpoint of the translocation t(7;19)(q35;p13) in cases of T-ALL. It is the LYL1 gene but not protein that is structurally altered following t(7;19), resulting in its head-to-head juxtaposition with the T-cell antigen receptor beta gene (TCR-beta). The translocation resulted in truncation of the LYL1 gene and production of abnormal-sized RNAs, bringing LYL1 gene under the regulatory control of TCR-beta, and thus resulting in its ectopic expression. In addition to the t(7;19)(q35;p13), other translocations are t(1;19)(p34;p13), t(1;19)(p32;p13), t(9;19)(q34;p13), t(9;19)(q32;p13), t(10;19)(q24;p13), t(11;19)(p13;p13), t(15;19)(q22;p13) etc; it is not known if all of the translocations lead to enhanced expression of LYL1. |
| Hybrid/Mutated Gene | The TCR-beta locus at 7q35 spans 685 kb (64-67 variable genes TRBV, 2 clusters of diversity, joining and constant segments). |
| Oncogenesis | As discussed above, the LYL1 gene was first identified at t(7;19)(q35;p13) associated T-ALL. However, over-expression of LYL1 has been reported in T-ALL cases without apparent chromosome aberration. LYL1, TAL1 and TAL2 constitute a discrete subgroup of helix-loop-helix proteins, each of which can potentially contribute to the development of T-ALL. Specific in vivo association between the bHLH and LIM proteins is implicated in human T cell leukemia. LYL1 can readily form heterodimers with E2A and NF-KappaB1 p105 protein. It is possible that LYL1 may function as a dominant-negative preventing the activation of the tumor suppressors like E2A. Ectopic expression of LYL1 may also be involved in myeloid leukemia. |
| | |
| Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy. |
| Asnafi V, Beldjord K, Libura M, Villarese P, Millien C, Ballerini P, Kuhlein E, Lafage-Pochitaloff M, Delabesse E, Bernard O, Macintyre E |
| Blood. 2004 ; 104 (13) : 4173-4180. |
| PMID 15054041 |
| |
| Muscarinic modulation of intrinsic burst firing in rat hippocampal neurons. |
| Azouz R, Jensen MS, Yaari Y |
| The European journal of neuroscience. 1994 ; 6 (6) : 961-966. |
| PMID 7952283 |
| |
| The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation. |
| Capron C, Lécluse Y, Kaushik AL, Foudi A, Lacout C, Sekkai D, Godin I, Albagli O, Poullion I, Svinartchouk F, Schanze E, Vainchenker W, Sablitzky F, Bennaceur-Griscelli A, Duménil D |
| Blood. 2006 ; 107 (12) : 4678-4686. |
| PMID 16514064 |
| |
| Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. |
| Ferrando AA, Neuberg DS, Dodge RK, Paietta E, Larson RA, Wiernik PH, Rowe JM, Caligiuri MA, Bloomfield CD, Look AT |
| Lancet. 2004 ; 363 (9408) : 535-536. |
| PMID 14975618 |
| |
| Physical interaction of the bHLH LYL1 protein and NF-kappaB1 p105. |
| Ferrier R, Nougarede R, Doucet S, Kahn-Perles B, Imbert J, Mathieu-Mahul D |
| Oncogene. 1999 ; 18 (4) : 995-1005. |
| PMID 10023675 |
| |
| Structure, chromosome mapping, and expression of the mouse Lyl-1 gene. |
| Kuo SS, Mellentin JD, Copeland NG, Gilbert DJ, Jenkins NA, Cleary ML |
| Oncogene. 1991 ; 6 (6) : 961-968. |
| PMID 2067848 |
| |
| lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif. |
| Mellentin JD, Smith SD, Cleary ML |
| Cell. 1989 ; 58 (1) : 77-83. |
| PMID 2752424 |
| |
| Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia. |
| Meng YS, Khoury H, Dick JE, Minden MD |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (11) : 1941-1947. |
| PMID 16094422 |
| |
| Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. |
| Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH, Baer R |
| The EMBO journal. 1994 ; 13 (20) : 4831-4839. |
| PMID 7957052 |
| |
| Nomenclature |
|---|
| HGNC (Hugo) | LYL1 6734 |
| Cards |
|---|
| Atlas | LYL1ID51ch19p13 |
| Entrez_Gene (NCBI) | LYL1 4066 LYL1 basic helix-loop-helix family member |
| Aliases | bHLHa18 |
| GeneCards (Weizmann) | LYL1 |
| Ensembl hg19 (Hinxton) | ENSG00000104903 [Gene_View] |
| Ensembl hg38 (Hinxton) | ENSG00000104903 [Gene_View] ENSG00000104903 [Sequence] chr19:13099028-13103160 [Contig_View] LYL1 [Vega] |
| ICGC DataPortal | ENSG00000104903 |
| TCGA cBioPortal | LYL1 |
| AceView (NCBI) | LYL1 |
| Genatlas (Paris) | LYL1 |
| WikiGenes | 4066 |
| SOURCE (Princeton) | LYL1 |
| Genetics Home Reference (NIH) | LYL1 |
| Genomic and cartography |
|---|
| GoldenPath hg38 (UCSC) | LYL1 - chr19:13099028-13103160 - 19p13.13 [Description] (hg38-Dec_2013) |
| GoldenPath hg19 (UCSC) | LYL1 - 19p13.13 [Description] (hg19-Feb_2009) |
| GoldenPath | LYL1 - 19p13.13 [CytoView hg19] LYL1 - 19p13.13 [CytoView hg38] |
| ImmunoBase | ENSG00000104903 |
| Mapping of homologs : NCBI | LYL1 [Mapview hg19] LYL1 [Mapview hg38] |
| OMIM | 151440 |
| Gene and transcription |
|---|
| Genbank (Entrez) | AI554151 AK311530 BC002796 BI908195 DB036722 |
| RefSeq transcript (Entrez) | NM_005583 |
| RefSeq genomic (Entrez) | |
| Consensus coding sequences : CCDS (NCBI) | LYL1 |
| Alternative Splicing Gallery | ENSG00000104903 |
| Gene Expression | LYL1 [ NCBI-GEO ] LYL1 [ EBI - ARRAY_EXPRESS ]
LYL1 [ SEEK ] LYL1 [ MEM ] |
| Gene Expression Viewer (FireBrowse) | LYL1 [ Firebrowse - Broad ] |
| SOURCE (Princeton) | Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60] |
| Genevestigator | Expression in : [tissues] [cell-lines] [cancer] [perturbations] |
| BioGPS (Tissue expression) | 4066 |
| GTEX Portal (Tissue expression) | LYL1 |
| Human Protein Atlas | ENSG00000104903-LYL1 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
|---|
| UniProt/SwissProt | P12980 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
| NextProt | P12980 [Sequence] [Exons] [Medical] [Publications] |
| With graphics : InterPro | P12980 |
| Splice isoforms : SwissVar | P12980 |
| PhosPhoSitePlus | P12980 |
| Domaine pattern : Prosite (Expaxy) | BHLH (PS50888) |
| Domains : Interpro (EBI) | bHLH_dom HLH_DNA-bd_sf TAL-like |
| Domain families : Pfam (Sanger) | HLH (PF00010) |
| Domain families : Pfam (NCBI) | pfam00010 |
| Domain families : Smart (EMBL) | HLH (SM00353) |
| Conserved Domain (NCBI) | LYL1 |
| DMDM Disease mutations | 4066 |
| Blocks (Seattle) | LYL1 |
| Superfamily | P12980 |
| Human Protein Atlas [tissue] | ENSG00000104903-LYL1 [tissue] |
| Peptide Atlas | P12980 |
| HPRD | 01046 |
| IPI | IPI00218258 IPI00979906 |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | P12980 |
| IntAct (EBI) | P12980 |
| FunCoup | ENSG00000104903 |
| BioGRID | LYL1 |
| STRING (EMBL) | LYL1 |
| ZODIAC | LYL1 |
| Ontologies - Pathways |
|---|
| QuickGO | P12980 |
| Ontology : AmiGO | nuclear chromatin RNA polymerase II regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific blood vessel maturation DNA binding protein binding nucleus regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II B cell differentiation positive regulation of transcription, DNA-templated protein dimerization activity definitive hemopoiesis |
| Ontology : EGO-EBI | nuclear chromatin RNA polymerase II regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific blood vessel maturation DNA binding protein binding nucleus regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II B cell differentiation positive regulation of transcription, DNA-templated protein dimerization activity definitive hemopoiesis |
| Pathways : KEGG | Transcriptional misregulation in cancer |
| NDEx Network | LYL1 |
| Atlas of Cancer Signalling Network | LYL1 |
| Wikipedia pathways | LYL1 |
| Orthology - Evolution |
|---|
| OrthoDB | 4066 |
| GeneTree (enSembl) | ENSG00000104903 |
| Phylogenetic Trees/Animal Genes : TreeFam | LYL1 |
| HOGENOM | P12980 |
| Homologs : HomoloGene | LYL1 |
| Homology/Alignments : Family Browser (UCSC) | LYL1 |
| Gene fusions - Rearrangements |
|---|
| Fusion : Mitelman | TRB/LYL1 [-/19p13.2] [t(7;19)(q34;p13)] |
| Fusion : TICdb | LYL1 [19p13.2] - TCR [] |
| Fusion : FusionGDB | 12966 |
| Fusion : Fusion_Hub | CXORF36--LYL1 FARSA--LYL1 HOX11--LYL1 LYL1--ETS2 LYL1--FKBP8 LYL1--LMO2 LYL1--TCR LYL1--TRB@ TRMT--LYL1 |
| Fusion : Quiver | LYL1 |
| Polymorphisms : SNP and Copy number variants |
|---|
| NCBI Variation Viewer | LYL1 [hg38] |
| dbSNP Single Nucleotide Polymorphism (NCBI) | LYL1 |
| dbVar | LYL1 |
| ClinVar | LYL1 |
| 1000_Genomes | LYL1 |
| Exome Variant Server | LYL1 |
| ExAC (Exome Aggregation Consortium) | ENSG00000104903 |
| GNOMAD Browser | ENSG00000104903 |
| Varsome Browser | LYL1 |
| Genetic variants : HAPMAP | 4066 |
| Genomic Variants (DGV) | LYL1 [DGVbeta] |
| DECIPHER | LYL1 [patients] [syndromes] [variants] [genes] |
| CONAN: Copy Number Analysis | LYL1 |
| Mutations |
|---|
| ICGC Data Portal | LYL1 |
| TCGA Data Portal | LYL1 |
| Broad Tumor Portal | LYL1 |
| OASIS Portal | LYL1 [ Somatic mutations - Copy number] |
| Somatic Mutations in Cancer : COSMIC | LYL1 [overview] [genome browser] [tissue] [distribution] |
| Somatic Mutations in Cancer : COSMIC3D | LYL1 |
| Mutations and Diseases : HGMD | LYL1 |
| LOVD (Leiden Open Variation Database) | Whole genome datasets |
| LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
| BioMuta | search LYL1 |
| DgiDB (Drug Gene Interaction Database) | LYL1 |
| DoCM (Curated mutations) | LYL1 (select the gene name) |
| CIViC (Clinical Interpretations of Variants in Cancer) | LYL1 (select a term) |
| intoGen | LYL1 |
| NCG5 (London) | LYL1 |
| Cancer3D | LYL1(select the gene name) |
| Impact of mutations | [PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
|---|
| OMIM | 151440 |
| Orphanet | |
| DisGeNET | LYL1 |
| Medgen | LYL1 |
| Genetic Testing Registry | LYL1
|
| NextProt | P12980 [Medical] |
| TSGene | 4066 |
| GENETests | LYL1 |
| Target Validation | LYL1 |
| Huge Navigator |
LYL1 [HugePedia] |
| snp3D : Map Gene to Disease | 4066 |
| BioCentury BCIQ | LYL1 |
| ClinGen | LYL1 |
| Clinical trials, drugs, therapy |
|---|
| Chemical/Protein Interactions : CTD | 4066 |
| Chemical/Pharm GKB Gene | PA30497 |
| Clinical trial | LYL1 |
| Miscellaneous |
|---|
| canSAR (ICR) | LYL1 (select the gene name) |
| Harmonizome | LYL1 |
| DataMed Index | LYL1 |
| Other database | http://www.cleanex.isb-sib.ch/cgi-bin/cleanex_query_result.pl?out_format=NICE&Entry_0=HGNC:6734 |
| Probes |
|---|
| Litterature |
|---|
| PubMed | 31 Pubmed reference(s) in Entrez |
| GeneRIFs | Gene References Into Functions (Entrez) |
| CoreMine | LYL1 |
| EVEX | LYL1 |
| GoPubMed | LYL1 |
| iHOP | LYL1 |
