| Note | |
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| Entity | t(11;14)(p13;q11)/T-cell leukaemia --> LMO2 - TCRD-A |
| Disease | Childhood T-cell ALL ; found in 5-10% of T-cell ALL. |
| Cytogenetics | A variant translocation t(7;11)(q35;p13) has been described. |
| Abnormal Protein | It was previously believed that LMO2 is activated after chromosomal translocation by association either the T-cell receptor a / T-cell receptor d (14q11) or T-cell receptor b gene (7q35). Chromosome breakpoints occur 25 kb upstream LMO2 gene, in a presumed transcriptional start site, inducing truncation of the promoter/control region and leading to inappropriate Lmo2 level especially in T-cells (abnormal T-cell differentiation). However, it becomes now very likely that removal of a negative regulatory element from the LMO2 locus, rather than juxtaposition to the TCRD enhancer, is the main determinant for LMO2 activation in the majority of t(11;14)(p13;q11) translocations. |
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| Entity | del(11)(p12p13) T-cell leukaemia |
| Disease | Childhood T-cell ALL; found in about 5% of T-cell ALL. |
| Cytogenetics | Cryptic deletion that varies in size. |
| Abnormal Protein | LMO2 is activated through a cryptic intrachromosomal deletion, del(11)(p12p13), in which a negative regulatory element (NRE), situated upstream of the LMO2 gene, is deleted. Removal of this NRE causes activation of the proximal promoter of the LMO2 gene leading to its ectopic expression. |
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| Entity | Germinal center B-cell lymphomas |
| Disease | Diffuse large-B-cell lymphomas, follicular lymphomas, Burkitt lymphomas, less often in other haematological malignancies. |
| Prognosis | LMO2 expression, together with BCL6, FN1, CCND2, SCYA3, and BCL2 expressions, is a predictor of outcome in diffuse large-B-cell lymphoma. |
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| Entity | Prostate cancer |
| Note | Expression of LMO2 is higher in prostate tumours samples than in the normal epithelium. Moreover, overexpression of LMO2 is significantly associated with advanced tumour stage, as well as with the development of distant metastasis. |
| Oncogenesis | LMO2 may play an important role in prostate cancer progression, possibly via repression of E-cadherin expression. |
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| Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2. |
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| The EMBO journal. 2004 ; 23 (14) : 2841-2852. |
| PMID 15215894 |
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| The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. |
| Boehm T, Foroni L, Kaneko Y, Perutz MF, Rabbitts TH |
| Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (10) : 4367-4371. |
| PMID 2034676 |
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| Different chromosomal breakpoints impact the level of LMO2 expression in T-ALL. |
| Dik WA, Nadel B, Przybylski GK, Asnafi V, Grabarczyk P, Navarro JM, Verhaaf B, Schmidt CA, Macintyre EA, van Dongen JJ, Langerak AW |
| Blood. 2007 ; 110 (1) : 388-392. |
| PMID 17360939 |
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| Expression of rhombotin 2 in normal and leukaemic haemopoietic cells. |
| Dong WF, Billia F, Atkins HL, Iscove NN, Minden MD |
| British journal of haematology. 1996 ; 93 (2) : 280-286. |
| PMID 8639417 |
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| Negative regulatory elements are present in the human LMO2 oncogene and may contribute to its expression in leukemia. |
| Hammond SM, Crable SC, Anderson KP |
| Leukemia research. 2005 ; 29 (1) : 89-97. |
| PMID 15541480 |
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| Human Bex2 interacts with LMO2 and regulates the transcriptional activity of a novel DNA-binding complex. |
| Han C, Liu H, Liu J, Yin K, Xie Y, Shen X, Wang Y, Yuan J, Qiang B, Liu YJ, Peng X |
| Nucleic acids research. 2005 ; 33 (20) : 6555-6565. |
| PMID 16314316 |
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| The Lim-only protein LMO2 acts as a positive regulator of erythroid differentiation. |
| Hansson A, Zetterblad J, van Duren C, Axelson H, Jönsson JI |
| Biochemical and biophysical research communications. 2007 ; 364 (3) : 675-681. |
| PMID 17964543 |
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| Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction. |
| Lécuyer E, Larivière S, Sincennes MC, Haman A, Lahlil R, Todorova M, Tremblay M, Wilkes BC, Hoang T |
| The Journal of biological chemistry. 2007 ; 282 (46) : 33649-33658. |
| PMID 17878155 |
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| Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. |
| Lossos IS, Czerwinski DK, Alizadeh AA, Wechser MA, Tibshirani R, Botstein D, Levy R |
| The New England journal of medicine. 2004 ; 350 (18) : 1828-1837. |
| PMID 15115829 |
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| The significance of LMO2 expression in the progression of prostate cancer. |
| Ma S, Guan XY, Beh PS, Wong KY, Chan YP, Yuen HF, Vielkind J, Chan KW |
| The Journal of pathology. 2007 ; 211 (3) : 278-285. |
| PMID 17167821 |
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| The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas. |
| Natkunam Y, Zhao S, Mason DY, Chen J, Taidi B, Jones M, Hammer AS, Hamilton Dutoit S, Lossos IS, Levy R |
| Blood. 2007 ; 109 (4) : 1636-1642. |
| PMID 17038524 |
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| TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). |
| Royer-Pokora B, Loos U, Ludwig WD |
| Oncogene. 1991 ; 6 (10) : 1887-1893. |
| PMID 1923511 |
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| 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 |
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| The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. |
| Wadman IA, Osada H, Grütz GG, Agulnick AD, Westphal H, Forster A, Rabbitts TH |
| The EMBO journal. 1997 ; 16 (11) : 3145-3157. |
| PMID 9214632 |
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| A novel transcript of the LMO2 gene, LMO2-c, is regulated by GATA-1 and PU.1 and encodes an antagonist of LMO2. |
| Wang Q, Zhang M, Wang X, Yuan W, Chen D, Royer-Pokora B, Zhu T |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2007 ; 21 (5) : 1015-1025. |
| PMID 17361224 |
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| The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis. |
| Yamada Y, Warren AJ, Dobson C, Forster A, Pannell R, Rabbitts TH |
| Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (7) : 3890-3895. |
| PMID 9520463 |
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| A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish. |
| Yang Z, Jiang H, Zhao F, Shankar DB, Sakamoto KM, Zhang MQ, Lin S |
| BMC developmental biology. 2007 ; 7 : page 97. |
| PMID 17708765 |
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