| Note | |
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| 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. |
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| Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy. |
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| The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation. |
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| Physical interaction of the bHLH LYL1 protein and NF-kappaB1 p105. |
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| PMID 10023675 |
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| Structure, chromosome mapping, and expression of the mouse Lyl-1 gene. |
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| PMID 2067848 |
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| 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. |
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| PMID 2752424 |
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| Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia. |
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| Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. |
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| PMID 7957052 |
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