LMO2

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The LMO2 gene at 11p13 codes for the 158 amino acid nucleation factor rhombotin-2. It assembles a multipartite transcriptional regulatory complex on gene regulatory regions via direct interaction with several DNA binding transcription factors. It regulates DNA replication in hematopoietic cells[1] and acts with LIM domain-binding protein 1 to maintain erythroid precursors in an immature state. LMO2 down-regulation is required for terminal erythroid differentiation.

A chromosomal aberration involving LMO2 appears to be a cause of a form of T-cell acute lymphoblastic leukaemia (T-ALL), being translocation t(11,14)(p13;q11).

In early gene therapy trials with ADA it was discovered that the viral agent used could cause T-cell leukaemia. It transpired the retrovirus vector integration was in proximity to the LMO2 protooncogene promoter, leading to aberrant transcription and expression of LMO2[2]. This has lead to the identification of safer viral vectors for gene therapy[3]. It is now accepted as a specific marker of T-lymphoblastic leukaemia/lymphoma[4]. So while there is evidence of it acting as a tumour promoter in haematological malignancies[5]. it may be a tumour suppressor in some carcinomas[6].

References

  1. Sincennes MC, Humbert M, Grondin B, Lisi V, Veiga DF, Haman A, Cazaux C, Mashtalir N, Affar el B, Verreault A, Hoang T. The LMO2 oncogene regulates DNA replication in hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America. 2016 Feb; 113(5):1393-1398.(Print-Electronic) (Link to article – subscription may be required.)
  2. Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, Radford I, Villeval JL, Fraser CC, Cavazzana-Calvo M, Fischer A. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. The New England journal of medicine. 2003 Jan; 348(3):255-256.(Print) (Link to article – subscription may be required.)
  3. Zhou S, Fatima S, Ma Z, Wang YD, Lu T, Janke LJ, Du Y, Sorrentino BP. Evaluating the Safety of Retroviral Vectors Based on Insertional Oncogene Activation and Blocked Differentiation in Cultured Thymocytes. Molecular therapy : the journal of the American Society of Gene Therapy. 2016 Jun; 24(6):1090-1099.(Print-Electronic) (Link to article – subscription may be required.)
  4. Jevremovic D, Roden AC, Ketterling RP, Kurtin PJ, McPhail ED. LMO2 Is a Specific Marker of T-Lymphoblastic Leukemia/Lymphoma. American journal of clinical pathology. 2016 Feb; 145(2):180-190.(Print-Electronic) (Link to article – subscription may be required.)
  5. Wiekmeijer AS, Pike-Overzet K, Brugman MH, van Eggermond MC, Cordes M, de Haas EF, Li Y, Oole E, van IJcken WF, Egeler RM, Meijerink JP, Staal FJ. Overexpression of LMO2 causes aberrant human T-Cell development in vivo by three potentially distinct cellular mechanisms. Experimental hematology. 2016 Sep; 44(9):838-849.e9.(Print-Electronic) (Link to article – subscription may be required.)
  6. Liu Y, Huang D, Wang Z, Wu C, Zhang Z, Wang D, Li Z, Zhu T, Yang S, Sun W. LMO2 attenuates tumor growth by targeting the Wnt signaling pathway in breast and colorectal cancer. Scientific reports. 2016 Oct; 6:36050.(Electronic) (Link to article – subscription may be required.)
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