Atlas of Genetics and Cytogenetics in Oncology and Haematology

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LYL1 (lymphoblastic leukemia derived sequence 1)

Written2006-12Yuesheng Meng, Mark D. Minden
Department of Cellular and Molecular Biology, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Canada

(Note : for Links provided by Atlas : click)


Other alias
LocusID (NCBI) 4066
Atlas_Id 51
Location 19p13.2  [Link to chromosome band 19p13]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
C2CD5 (12p12.1) / LYL1 (19p13.13)LYL1 (19p13.13) / TRBV20OR9-2 (-)LYL1 (19p13.2) / TAL1 (1p33)
LYL1 (19p13.2) / TRBV20OR9-2 (-)TRMU (22q13.31) / LYL1 (19p13.2)


Note DNA size: 3.83 kb; mRNA size: 1492 bp; Exons: 4.
Description Location of the LYL1 gene, identified by Non-random chromosomal translocation t(7;19)(q35;p13) associated with T-cell acute lymphoblastic leukemia (T-ALL), was mapped to the short arm of chromosome 19 (19p13) by in situ hybridization.
Transcription Expression levels of LYL1 are comparatively higher in normal bone marrow, spleen, lung, thymus and spinal cord tissues. Ectopic transcription is observed in T-lymphoblastic and myeloblastic leukemic cells.


Description LYL1 encodes a basic helix-loop-helix (bHLH) protein, with 267 amino acids and molecular weight of 28628 Da.
Localisation Subcellular location is potentially intracellular (nucleus). However, ectopic protein staining was observed in cytoplasm of myeloid leukemia cells with immunohistochemistry.
Function Recent studies show that LYL1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation. Overexpression of LYL1 is implicated in the pathogenesis of T-ALL as well as myeloid malignancies (see below, disease implications). The LYL1 protein is a transcription factor (TF), structurally and functionally similar to another bHLH protein TAL1/SCL which is also implicated in T-ALL. Expression of both LYL1 and TAL1/SCL are regulated by the Ets and GATA factors; However, ectopic expression of SCL but not Lyl1 can rescue haematopoietic differentiation in SCL(-/-) ES-cells, providing a molecular explanation for the vastly different phenotypes of SCL(-/-) and Lyl1(-/-) mouse embryos.
Efficient DNA binding of LYL1 requires dimerization with proteins. Specific in vivo association was observed between the bHLH and LIM proteins (LMO1 and LMO2). LYL1 readily forms heterodimeric complexes with E2A and may function as a dominant-negative preventing the activation of E2A responsive genes. LYL1 interacts also with p105 the precursor of NF-KappaB1 p50.
Homology The bHLH region of LYL1 and TAL1/SCL proteins show 82% amino acid identity, suggesting that these two proteins share at least some target genes and biologic functions. However, LYL-1 and TAL1diverge largely outside the bHLH region and display a distinct expression pattern in hematopoietic cells. Mouse Lyl-1 protein is 78% identical to human LYL1.

Implicated in

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


This paper should be referenced as such :
Minden, MD ; Meng, Y
LYL1 (lymphoblastic leukemia derived sequence 1)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):99-101.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 9 ]
  Pediatric T-Cell Acute Lymphoblastic Leukemia
t(7;19)(q34;p13) TRB/LYL1
t(7;19)(q34;p13) LYL1/TRB
Pediatric T-Cell Acute Lymphoblastic Leukemia
t(1;7)(p36;p12) IKZF1/PRDM16
t(7;9)(q34;q32) TRB/TAL2
t(7;19)(q34;p13) TRB/LYL1
T-lineage acute lymphoblastic leukemia (T-ALL)
t(7;19)(q34;p13) LYL1/TRB

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)4066
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
Other database
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 18 17:41:49 CEST 2018

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