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The TCL1 family of oncoproteins: co-activators of transformation

Nature Reviews Cancer volume 5, pages 640–648 (2005)Cite this article

An Erratum to this article was published on 01 September 2005

Abstract

The T-cell leukaemia/lymphoma 1 (TCL1)-family oncoproteins augment AKT signal transduction and enhance cell proliferation and survival. Chromosome rearrangements, faulty developmental silencing and Epstein–Barr virus infection appear to dysregulate the expression of TCL1-family genes, provoking several important types of lymphocyte cancer. A key role for TCL1 proteins in cell transformation has been established in studies of transgenic mouse models, which develop a unique spectrum of T- and B-cell malignancies. How TCL1 proteins are regulated and dysregulated, how they promote transformation and the potential for therapies modelled on TCL1 interactions have important implications for understanding and treating lymphocyte cancers.

Key Points

  • The T-cell leukaemia/lymphoma 1 (TCL1) gene family consists of three genes in humans and seven genes in mice and these encode for small, intracellular, β-barrel-shaped proteins. Members of the human TCL1 family are known to bind and augment AKT kinase activity, thereby regulating signal transduction from the environment.

  • Normal expression of TCL1 family members seems to be limited mainly to early embryogenesis, germ cells, specific fetal and adult tissues, and precursor/immature T and B lymphocytes.

  • Dysregulated TCL1-family gene expression in T cells, by chromosome rearrangements, or in B cells, possibly by Epstein–Barr virus infection or aberrant silencing, enhances cell proliferation and survival and leads to cell transformation following a prolonged latency.

  • Transgenic mice that abberantly express TCL1 genes provide unique models of mature human lymphoid malignancies (including T-cell prolymphocytic leukaemia, Burkitt lymphoma, diffuse large B-cell lymphoma, rare follicular lymphoma, and B-cell chronic lymphocytic leukaemia) that have not been seen after other genetic, viral or environmental manipulations.

  • The precise mechanism for TCL1-mediated transformation is not resolved. There are potentially relevant AKT target proteins in the cytosol and possibly the nucleus. To determine how TCL1 proteins cause cancer, it is crucially important that we determine the mechanisms of TCL1-family gene regulation and dysregulation, understand potential AKT-independent effects, discover complementing alterations required for malignancy, and determine transforming activity beyond lymphocytes.

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Figure 1: Dysregulated TCL1A expression in mature B-cell and T-cell cancers.
Figure 2: TCL1 family protein structure and binding surfaces.
Figure 3: TCL1 co-activation of AKT.
Figure 4: Modelled interaction between TCL1A and AKT at the membrane and the blocking of AKT activation by a TCL1A-derived peptide.

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References

  1. Virgilio, L. et al. Identification of the TCL1 gene involved in T-cell malignancies. Proc. Natl Acad. Sci. USA 91, 12530–12534 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Madani, A. et al. Expression of p13MTCP1 is restricted to mature T-cell proliferations with t(X;14) translocations. Blood 87, 1923–1927 (1996).

    CAS  PubMed  Google Scholar 

  3. Narducci, M. G. et al. The murine Tcl1 oncogene: embryonic and lymphoid cell expression. Oncogene 15, 919–926 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Pekarsky, Y. et al. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc. Natl Acad. Sci. USA 97, 3028–3033 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Laine, J., Kunstle, G., Obata, T., Sha, M. & Noguchi, M. The protooncogene TCL1 is an Akt kinase co-activator. Mol. Cell 6, 395–407 (2000). Together with reference 4, this article shows that TCL1 binds and augments AKT-kinase activity.

    Article  CAS  PubMed  Google Scholar 

  6. French, S. W. et al. A modeled hydrophobic domain on the TCL1 oncoprotein mediates association with AKT at the cytoplasmic membrane. Biochemistry 41, 6376–6382 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Auguin, D. et al. Structural basis for the co-activation of protein kinase B by T-cell leukemia-1 (TCL1) family proto-oncoproteins. J. Biol. Chem. 279, 35890–35902 (2004). This article provides a structural model for the TCL1–AKT interaction stabilized at the cytoplasmic membrane.

    Article  CAS  PubMed  Google Scholar 

  8. Narducci, M. G. et al. TCL1 participates in early embryonic development and is overexpressed in human seminomas. Proc. Natl Acad. Sci. USA 99, 11712–11717 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kang, S. M. et al. Impaired T and B cell development in Tcl1 deficient mice. Blood 105, 1288–1294 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Kiss, C. et al. T cell leukemia I oncogene expression depends on the presence of Epstein-Barr virus in the virus-carrying Burkitt lymphoma lines. Proc. Natl Acad. Sci. USA 100, 4813–4818 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. French, S. W. et al. Sp1 transactivation of the TCL1 oncogene. J. Biol. Chem. 278, 948–955 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Virgilio, L. et al. Deregulated expression of TCL1 causes T cell leukemia in mice. Proc. Natl Acad. Sci. USA 95, 3885–3889 (1998). Together with references 13–15, this paper shows that TCL1 dysregulation transforms T- and B-lymphocytes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gritti, C. et al. Transgenic mice for MTCP1 develop T-cell prolymphocytic leukemia. Blood 92, 368–373 (1998). Provides a genetic model for human B-CLL by dysregulated TCL1 expression in B cells.

    CAS  PubMed  Google Scholar 

  14. Bichi, R. et al. Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression. Proc. Natl Acad. Sci. USA 99, 6955–6960 (2002). Provides a genetic model for human GC B-cell transformation by the dysregulated expression of TCL1 in B- and T-lineage cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hoyer, K. K. et al. Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma. Proc. Natl Acad. Sci. USA 99, 14392–14397 (2002). Provides a genetic model for human GC B-cell transformation by the dysregulated expression of TCL1 in B- and T-lineage cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Russo, G. et al. Molecular analysis of a t(7;14)(q35;q32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia. Cell 53, 137–144 (1988).

    Article  CAS  PubMed  Google Scholar 

  17. Pekarsky, Y., Hallas, C. & Croce, C. M. Molecular basis of mature T-cell leukemia. JAMA 286, 2308–2314 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Pekarsky, Y., Hallas, C. & Croce, C. M. The role of TCL1 in human T-cell leukemia. Oncogene 20, 5638–5643 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Teitell, M. A. in Wiley's Encyclopedia of Molecular Medicine (ed. Creighton, T. E.) 3106–3108 (J. Wiley & Sons, New York, 2002).

    Google Scholar 

  20. Pekarsky, Y., Zanesi, N., Aqeilan, R. & Croce, C. M. Tcl1 as a model for lymphomagenesis. Hematol. Oncol. Clin. North Am. 18, 863–79, ix (2004).

    Article  PubMed  Google Scholar 

  21. Stern, M. H. et al. MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor α/δ locus in mature T cell proliferations. Oncogene 8, 2475–2483 (1993).

    CAS  PubMed  Google Scholar 

  22. Pekarsky, Y., Hallas, C., Isobe, M., Russo, G. & Croce, C. M. Abnormalities at 14q32. 1 in T cell malignancies involve two oncogenes. Proc. Natl Acad. Sci. USA 96, 2949–2951 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sugimoto, J., Hatakeyama, T., Narducci, M. G., Russo, G. & Isobe, M. Identification of the TCL1/MTCP1-like 1 (TML1) gene from the region next to the TCL1 locus. Cancer Res. 59, 2313–2317 (1999).

    CAS  PubMed  Google Scholar 

  24. Hallas, C. et al. Genomic analysis of human and mouse TCL1 loci reveals a complex of tightly clustered genes. Proc. Natl Acad. Sci. USA 96, 14418–14423 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Minami, N., Sasaki, K., Aizawa, A., Miyamoto, M. & Imai, H. Analysis of gene expression in mouse 2-cell embryos using fluorescein differential display: comparison of culture environments. Biol. Reprod. 64, 30–35 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Teague, T. K. et al. Activation changes the spectrum but not the diversity of genes expressed by T cells. Proc. Natl Acad. Sci. USA 96, 12691–12696 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Herling, M., Teitell, M. A., Shen, R. R., Medeiros, L. J. & Jones, D. TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumours of skin. Blood 101, 5007–5009 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. Teitell, M. et al. TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues. Proc. Natl Acad. Sci. USA 96, 9809–9814 (1999). This study is the first to provide a potential oncogenic role for dysregulated TCL1 in human B-cell tumours.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Said, J. W. et al. TCL1 oncogene expression in B cell subsets from lymphoid hyperplasia and distinct classes of B cell lymphoma. Lab. Invest. 81, 555–564 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Muschen, M. et al. Molecular portraits of B cell lineage commitment. Proc. Natl Acad. Sci. USA 99, 10014–10019 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Narducci, M. G. et al. TCL1 is overexpressed in patients affected by adult T-cell leukemias. Cancer Res. 57, 5452–5456 (1997).

    CAS  PubMed  Google Scholar 

  32. Hoyer, K. K. et al. TCL1 modulates TCR signal strength and IFNγ levels through PI3K and PKC pathway activation. J. Immunol. 175, 864–873 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Soulier, J. et al. The MTCP-1/c6. 1B gene encodes for a cytoplasmic 8 kD protein overexpressed in T cell leukemia bearing a t(X;14) translocation. Oncogene 9, 3565–3570 (1994).

    CAS  PubMed  Google Scholar 

  34. Yuille, M. R. et al. TCL1 is activated by chromosomal rearrangement or by hypomethylation. Genes Chromosom. Cancer 30, 336–341 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Chun, H. H. et al. TCL-1, MTCP-1 and TML-1 gene expression profile in non-leukemic clonal proliferations associated with ataxia-telangiectasia. Int. J. Cancer 97, 726–731 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Narducci, M. G. et al. Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues. Cancer Res. 60, 2095–2100 (2000).

    CAS  PubMed  Google Scholar 

  37. Petrella, T. et al. TCL1 and CLA expression in agranular CD4/CD56 hematodermic neoplasms (blastic NK-cell lymphomas) and leukemia cutis. Am. J. Clin. Pathol. 122, 307–313 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Klein, U. et al. Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J. Exp. Med. 194, 1625–1638 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bell, A. & Rickinson, A. B. Epstein-Barr virus, the TCL-1 oncogene and Burkitt's lymphoma. Trends Microbiol. 11, 495–497 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Fu, T. B. et al. Characterization and localization of the TCL-1 oncogene product. Cancer Res. 54, 6297–6301 (1994).

    CAS  PubMed  Google Scholar 

  41. Hoh, F. et al. Crystal structure of p14TCL1, an oncogene product involved in T-cell prolymphocytic leukemia, reveals a novel β-barrel topology. Structure 6, 147–155 (1998). Shows that members of the TCL1 gene family encode proteins that have a novel β-barrel structure.

    Article  CAS  PubMed  Google Scholar 

  42. Fu, Z. Q. et al. Crystal structure of MTCP-1: implications for role of TCL-1 and MTCP-1 in T cell malignancies. Proc. Natl Acad. Sci. USA 95, 3413–3418 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Petock, J. M. et al. Structure of murine Tcl1 at 2.5 A resolution and implications for the TCL oncogene family. Acta Crystallogr. D Biol. Crystallogr. 57, 1545–1551 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Madani, A. et al. The 8 kD product of the putative oncogene MTCP-1 is a mitochondrial protein. Oncogene 10, 2259–2262 (1995).

    CAS  PubMed  Google Scholar 

  45. Bellacosa, A., Testa, J. R., Staal, S. P. & Tsichlis, P. N. A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Science 254, 274–277 (1991).

    Article  CAS  PubMed  Google Scholar 

  46. Datta, S. R., Brunet, A. & Greenberg, M. E. Cellular survival: a play in three Akts. Genes Dev. 13, 2905–2927 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Chan, T. O., Rittenhouse, S. E. & Tsichlis, P. N. AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu. Rev. Biochem. 68, 965–1014 (1999).

    Article  CAS  PubMed  Google Scholar 

  48. Brazil, D. P. & Hemmings, B. A. Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem. Sci. 26, 657–664 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Hill, M. M., Feng, J. & Hemmings, B. A. Identification of a plasma membrane Raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1. Curr. Biol. 12, 1251–1255 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Sarbassov, D. D., Guertin, D. A., Ali, S. M. & Sabatini, D. M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098–1101 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Burgering, B. M. & Coffer, P. J. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 376, 599–602 (1995).

    Article  CAS  PubMed  Google Scholar 

  52. Franke, T. F., Kaplan, D. R., Cantley, L. C. & Toker, A. Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3, 4-bisphosphate. Science 275, 665–668 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Delcommenne, M. et al. Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc. Natl Acad. Sci. USA 95, 11211–11216 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Toker, A. & Newton, A. C. Akt/protein kinase B is regulated by autophosphorylation at the hypothetical PDK-2 site. J. Biol. Chem. 275, 8271–8274 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Persad, S. et al. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J. Biol. Chem. 276, 27462–27469 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Bayascas, J. R. & Alessi, D. R. Regulation of Akt/PKB Ser473 Phosphorylation. Mol. Cell 18, 143–145 (2005).

    Article  CAS  PubMed  Google Scholar 

  57. Laine, J., Kunstle, G., Obata, T. & Noguchi, M. Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family. J. Biol. Chem. 277, 3743–3751 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. Kunstle, G. et al. Identification of Akt association and oligomerization domains of the Akt kinase co-activator TCL1. Mol. Cell. Biol. 22, 1513–1525 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gold, M. R. Akt is TCL-ish: implications for B-cell lymphoma. Trends Immunol. 24, 104–108 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Hiromura, M. et al. Inhibition of Akt kinase activity by a peptide spanning the βA strand of the protooncogene TCL1. J. Biol. Chem. 279, 53407–53418 (2004). Shows the first, specific in vitro AKT kinase inhibitor, which consists of a 15-amino acid peptide stretch from the AKT binding domain βA strand of TCL1.

    Article  CAS  PubMed  Google Scholar 

  61. Pekarsky, Y. et al. Akt phosphorylates and regulates the orphan nuclear receptor Nur77. Proc. Natl Acad. Sci. USA 98, 3690–3694 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lin, B. et al. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 116, 527–540 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Malstrom, S., Tili, E., Kappes, D., Ceci, J. D. & Tsichlis, P. N. Tumour induction by an Lck-MyrAkt transgene is delayed by mechanisms controlling the size of the thymus. Proc. Natl Acad. Sci. USA 98, 14967–14972 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Morse, H. C., 3rd et al. Bethesda proposals for classification of lymphoid neoplasms in mice. Blood 100, 246–258 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Egle, A., Harris, A. W., Bath, M. L., O'Reilly, L. & Cory, S. VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia. Blood 103, 2276–2283 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Ramuz, O. et al. Identification of TCL1A as an immunohistochemical marker of adverse outcome in diffuse large B-cell lymphomas. Int. J. Oncol. 26, 151–157 (2005).

    CAS  PubMed  Google Scholar 

  67. Suzuki, A. et al. Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. J. Exp. Med. 197, 657–667 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Anzelon, A. N., Wu, H. & Rickert, R. C. Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function. Nature Immunol. 4, 287–294 (2003).

    CAS  Google Scholar 

  69. Maira, S. M. et al. Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane. Science 294, 374–380 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Gao, T., Furnari, F. & Newton, A. C. PHLPP: A phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumour growth. Mol. Cell 18, 13–24 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Bayascas, J. R. & Alessi, D. R. Regulation of Akt/PKB Ser473 phosphorylation. Mol. Cell 18, 143–145 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Milburn, C. C. et al. Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change. Biochem. J. 375, 531–538 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Thomas, C. C., Deak, M., Alessi, D. R. & van Aalten, D. M. High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate. Curr. Biol. 12, 1256–1262 (2002).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

I apologize to those authors whose important primary papers were not cited but were instead referenced in the cited reviews. I thank C. M. Koehler and C. S. Malone (both at the University of California, Los Angeles) for helpful comments. The Teitell lab is supported by the National Institutes of Health, the Margaret E. Early Medical Research Trust, and the Center for Cell Mimetic Studies (CMISE, a NASA University Research, Engineering, and Technology Institute). M.A.T. is a Leukemia and Lymphoma Society Scholar.

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  1. Department of Pathology and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 675 Charles Young Drive South, 4-762 MacDonald Research Laboratories, Los Angeles, 90095-1732, California, USA

    Michael A. Teitell

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DATABASES

Entrez Gene

AKT1

AKT2

AKT3

BCL2

CTMP

MTCP1

Mtcp1

PHLPP

PP2A

TCL1A

TCL1B

Tcl1b1

Tcl1b2

Tcl1b3

Tcl1b4

Tcl1b5

TR3

Glossary

AKT

In 1991, v-Akt was cloned as the transforming oncogene of the AKT8 murine leukaemia retrovirus. Three mammalian AKT homologues control cell growth, survival, glucose metabolism, transcription and cell migration.

ATAXIA TELANGIECTASIA

An autosomal recessive neurodegenerative disorder with onset in early childhood, that results from mutations in the ataxia telangiectasia mutated (ATM) gene. Patients are predisposed to develop cancer, especially leukaemia and lymphoma.

BLASTOCYST

Post-fertilization early embryonic structure composed of an inner cell mass surrounded by a fluid-filled cavity formed of extra-embryonic tissue. The inner cell mass will become the definitive offspring.

PRO-B CELL

Early-stage B-cell precursor within the bone marrow, in which developing B-cells first begin to genetically rearrange their immunoglobulin genes in preparation for making functional antibodies.

GERMINAL CENTRE B CELLS

B cells in peripheral lymphoid organs, such as lymph node and spleen, which undergo T-cell-dependent antigenic stimulation in a germinal center. A germinal centre is a secondary lymphoid structure in which T-cell-dependent antigens drive B-cell antibody affinity maturation in a genetically error-prone process

THYMOCYTE

Precursors of T cells, derived from the thymus.

PLASMA CELL

The final product of B-cell development, a plasma cell is the major antibody manufacturing and secreting cell of the body.

PERIPHERAL T CELL

A T cell that has survived positive and negative selection exits the thymus and enters the circulation as a functional CD4+ or CD8+ T cell.

CPG-RICH ISLAND

A genomic region of about 200 base pairs that contains more than the theoretical, expected frequency of cytosine–guanine dinucleotides.

T-CELL PROLYMPHOCYTIC LEUKAEMIA

An aggressive leukaemia of peripheral T cells that frequently contains chromosome rearrangements that activate TCL1A or MTCP1.

SEMINOMA

Tumour of primitive germ cells in male testes. This tumour is identical to dysgerminoma in female ovaries.

DYSGERMINOMA

Tumour of primitive germ cells in female ovaries. This tumour is identical to seminoma in male testes.

CD4/CD56 HAEMATODERMIC NEOPLASM

Also termed CD4/CD56 blastic tumour of skin, this entity is a rare and aggressive malignancy probably derived from the transformation of a plasmacytoid dendritic cell.

MANTLE ZONE

Region surrounding a GC central follicle in which pre-GC B-cells are prevented from entering the GC reaction for B-cell antibody affinity maturation by having an incorrect immunoglobulin for the inciting T-dependent antigen.

LIPID RAFT

A putative detergent-resistant microdomain of the plasma membrane that might concentrate specific molecules and complexes to facilitate key membrane processes, including signal transduction.

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Teitell, M. The TCL1 family of oncoproteins: co-activators of transformation. Nat Rev Cancer 5, 640–648 (2005). https://doi.org/10.1038/nrc1672

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