| Written | 2007-07 | Pieter Van Vlierberghe, Jules PP Meijerink |
| ErasmusMC/Sophia Children Hospital, Pediatric Oncology/Hematology, Rotterdam, The Netherlands |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9837/3 T lymphoblastic leukaemia/lymphoma |
| Atlas_Id | 1351 |
| Clinics and Pathology |
| Disease | T-cell acute lymphoblastic leukemia (T-ALL). |
| Epidemiology | About 5% of T-ALL patients. |
| Prognosis | Currenlty, no relation between the cryptic deletion, del(11)(p12p13), and prognosis could be established. This could be due to the limited patient numbers in the study. |
| Genetics |
| The cryptic deletion, del(11)(p12p13) was identified using microarray-based comparative genome hybridisation (array-CGH). The deleted region is about 3 Mb in size and the telomeric breakpoint of these deletions is situated in or near the LMO2 oncogene. Variances in the centromeric breakpoints is detected. |
| Cytogenetics |
| Variants | One of the T-ALL patients showed a cryptic deletion, del(11)(p12p13), that did not target the LMO2 oncogene. Indeed, this case showed no ectopic LMO2 expression. Therefore, this genomic region could potentially contain a tumor supressor gene that also contributes to T-ALL pathogenesis. |
| Genes involved and Proteins |
| Gene Name | LMO2 (LIM domain only 2 (rhombotin-like 1)) |
| Location | 11p13 |
| Protein | LMO2 encodes a protein that participates in the transcription factor complex, which includes E2A, TAL1, GATA1, and LDB1 in erythroid cells. Within this transcription complex, LMO2 mediates the protein-protein interactions by recruiting LDB1, whereas TAL1, GATA1, and E2A regulate the binding to specific DNA target sites. This complex regulates the expression of several genes in various cellular backgrounds including C-KIT, EKLF, and RALDH. In normal T-cell development, LMO2 is expressed in immature CD4/CD8 double-negative thymocytes, and is down-regulated during T-cell maturation. |
| Result of the chromosomal anomaly |
| Note | Ectopic expression of the LMO2 oncogene due to the removal of a negative regulatory element situated upstream of the LMO2 gene, leading to activation of the proximal LMO2 promoter. In one T-ALL case, this recurrent deletion resulted in a RAG2-LMO2 fusion gene, bringing the LMO2 gene under the control of RAG2 promoter sequences. However, it was shown that promoter substitution was not the main activational mechanism as none of the other del(11)(p12p13) positive cases showed a similar RAG2-LMO2 fusion gene. In addition, RQ-PCR analysis revealed that the expression of the RAG2-LMO2 fusion is much lower than the wildtype LMO2 expression from the proximal LMO2 gene promoter. |
| Bibliography |
| The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia. |
| Van Vlierberghe P, van Grotel M, Beverloo HB, Lee C, Helgason T, Buijs-Gladdines J, Passier M, van Wering ER, Veerman AJ, Kamps WA, Meijerink JP, Pieters R |
| Blood. 2006 ; 108 (10) : 3520-3529. |
| PMID 16873670 |
| Citation |
| This paper should be referenced as such : |
| Van, Vlierberghe P ; Meijerink, JPP |
| del(11)(p12p13) |
| Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):243-243. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/del11p12p13ID1351.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Genes | LMO2 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| del(11)(p12p13) LMO2 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Sep 18 17:18:26 CEST 2017 |
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