Disease relevance of LYL1

• The LYL1 gene was first identified upon the molecular characterization of the t(7;9)(q35;p13) translocation associated with some human T-cell acute leukemias (T-ALLs) [1].
• The TAL-1/SCL and LYL-1 genes encode two closely related basic helix-loop-helix transcription factors involved in child T-acute lymphoblastic leukemia through chromosomal rearrangements and transcriptional deregulation [2].
• TAL2 potentially encodes a basic helix-loop-helix motif that is highly related to those specified by TAL1 and LYL1, distinct genes that have also been implicated in T-ALL [3].
• LYL1 is a basic helix-loop-helix (HLH) protein that was originally discovered because of its translocation into the beta T-cell receptor locus in an acute lymphoblastic leukemia [4].
• Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia [5].

High impact information on LYL1

• This review focuses on two of these family members: SCL and LYL-1 [6].
• TAL1, TAL2 and LYL1 encode a unique subgroup of basic helix-loop-helix (bHLH) proteins that share exceptional homology in their bHLH sequences [7].
• LMO2 was more frequently coexpressed with LYL1, predominantly in IM0/delta/gamma adult cases, than with TAL1 [8].
• Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells [4].
• LYL1 is expressed in many hematolymphoid cells, with the notable exceptions of thymocytes and T cells [4].

Biological context of LYL1

• We describe here the expression pattern of lyl-1 in mouse embryos from 7 to 14 days post coitus using in situ hybridization, as well as beta-Galactosidase (beta-Gal) expression in lyl-1-lacZ knock-in embryos, which express a C-terminally truncated Lyl-1 protein fused to the beta-Galactosidase (Lyl-1Delta/beta-Gal) [2].
• Using the yeast two-hybrid system to screen a cDNA library constructed from B cells, we identified the E-box-binding proteins E12 and E47 as potential lymphoid dimerization partners for LYL1 [4].
• We conclude that LYL1 has the properties of a lineage- and differentiation-specific HLH protein that contributes to T-cell neoplasia through its deregulated expression following chromosomal translocation [9].
• The mouse Lyl-1 gene was cloned and shown to consist of four exons with extensive nucleotide and structural homology to the human LYL1 gene [9].
• In a human T ALL cell line carrying a translocation that juxtaposed LYL1 with the beta TCR gene, the translocated LYL1 gene was transcriptionally active whereas the nontranslocated gene was transcriptionally silent [9].

Anatomical context of LYL1

• Ectopic expression of LYL1 in a human T cell line caused a significant decrease in NF-kappaB-dependent transcription, associated with a reduced level of NF-kappaB1 proteins [1].
• Immunoprecipitation analyses showed that in T-ALL and other cell lines, endogenous LYL1 exists in a complex with E2a proteins [4].
• Overexpression of LYL1 in U937 cells blocked all-trans retinoic acid-induced monocytic differentiation [5].
• Forced expression of LYL1 in K562 cells enhanced spontaneous and hemin-induced erythroid differentiation but blocked spontaneous as well as PMA-induced megakaryocytic differentiation [5].
• Using real-time quantitative RT-PCR assay, we found that the expression of LYL1 was at higher levels in the majority cases of acute myeloblastic leukemia (AML) or myelodysplastic syndrome when compared to normal bone marrow [5].

Other interactions of LYL1

• Patients with HOX11-positive lymphoblasts have an excellent prognosis when treated with modern combination chemotherapy, while cases at high risk of early failure are included largely in the TAL1- and LYL1-positive groups [10].
• Biochemical studies indicated that the interaction was mediated by the bHLH motif of LYL1 and the ankyrin-like motifs of p105 [1].
• 3. These two regulatory genes are thus assigned to a region of high gene density and RFX1 is close to another DNA-binding factor, LYL1 [11].
• The E2A gene is involved by the t(1;19)(q23;p13) in acute pre-B-cell leukemias and the LYL1 gene is structurally altered by a t(7;19)(q34;p13) in T-cell ALL [12].

Analytical, diagnostic and therapeutic context of LYL1

• To determine whether LYL1 had an affect on the phenotype and behavior of myeloid cells, we introduced full-length LYL1 cDNA into K562 cells using electroporation and U937 cells with retroviral infection [5].

References