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Gene Review

MLANA  -  melan-A

Homo sapiens

Synonyms: Antigen LB39-AA, Antigen SK29-AA, MART-1, MART1, Melanoma antigen recognized by T-cells 1, ...
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Disease relevance of MLANA

  • We have shown previously that peripheral blood lymphocytes (PBL) of patients with metastatic melanoma include cytotoxic T-cell clones that recognize Melan-A/MART-1 in a HLA-A2-restricted fashion [1].
  • Metastases increasing in size over time showed a loss of Melan A/MART-1 expression in the presence of CTL in one patient [2].
  • Our study shows that angiomyolipomas express the melanocyte-associated antigens Melan-A and gp-100 at the protein and at the mRNA level, suggesting a true expression of these antigens rather than cross-reacting epitopes [3].
  • Our results demonstrate that Melan-A and tyrosinase are sensitive and specific markers to distinguish epithelioid melanocytic nevi from epithelioid histiocytic tumors [4].
  • CONCLUSION: The sclerotic/desmoplastic and hypopigmented blue nevi were uniformly positive for Melan-A, while the vast majority of DMM were negative in their spindle cell compartments [5].
  • Even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients [6].

High impact information on MLANA

  • We identified circulating CD8+ T-cell populations specific for the tumor-associated antigens (TAAs) MART-1 (27-35) or tyrosinase (368-376) in six of eleven patients with metastatic melanoma using peptide/HLA-A*0201 tetramers [7].
  • Postthymic replicative history of Melan-A/MART-1-specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo [8].
  • Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single-positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults [8].
  • Current strategies for the immunotherapy of melanoma include augmentation of the immune response to tumor antigens represented by melanosomal proteins such as tyrosinase, gp100, and MART-1 [9].
  • In contrast to skin biopsies obtained from the patient before T cell infusion, postinfusion biopsies demonstrated loss of MART-1 expression, evidence of melanocyte damage, and the complete absence of melanocytes in affected regions of the skin [9].

Chemical compound and disease context of MLANA

  • Their SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and eosin staining and immunohistochemistry [10].
  • Analysis of melanoma cells in peripheral blood by reverse transcription-polymerase chain reaction for tyrosinase and MART-1 after mononuclear cell collection with cell preparation tubes: a comparison with the whole blood guanidinium isothiocyanate RNA isolation method [11].
  • The discriminatory immunostaining pattern with the 'MCW Melanoma Cocktail' (a mixture of MART-1 {1:500}, Melan- A {1:100}, and Tyrosinase {1:50} monoclonal antibodies) allows intraoperative immunocytochemical evaluation of imprint smears of SLNs for melanoma metastases [12].
  • Originally studied as a melanoma marker, Melan-A, as detected by the murine monoclonal antibody, A103, has gained recent attention as a marker for steroid-producing cells [13].
  • We compared the new melanoma markers, Melan-A (clone A103) and MART-1 (clone M2-7C10), with S-100 protein and HMB-45, by examining 77 formalin-fixed paraffin-embedded sections of sentinel lymph nodes from 13 cases of primary cutaneous melanoma [14].

Biological context of MLANA


Anatomical context of MLANA


Associations of MLANA with chemical compounds

  • According to the authors' experience the antibody against KBA 62 has shown to be the most effective antibody followed by the antibodies against MART-1 (Melan A) and NKI/C3 [24].
  • Stably growing hybrid antigen-presenting cells (HAPC) expressing HLA-DR and HLA-A2 (or HLA-A30/31), and melanoma-associated antigens (MART-1, gp100) were selected by a double strategy of immunomagnetic MACS and neomycin selection [25].
  • The tumor cells strongly expressed S100 protein, gp100 (HMB-45), melan A, and tyrosine antibodies (Fig. 2C,D) [26].
  • Indium-111 labeling of Melan-A-specific CTL demonstrated localization of transferred CTL to metastatic sites as early as 48 h after injection [27].
  • Here we show that Melan-A is a single-pass membrane protein with an NH(2) terminus exposed to the lumen of the exocytic compartment [28].

Physical interactions of MLANA

  • We show that MART-1 forms a complex with Pmel17 and affects its expression, stability, trafficking, and the processing which is required for melanosome structure and maturation [22].
  • We point out the differences between the cutaneous and renal forms of angiomyolipoma, and conclude that the cutaneous lesion is distinct from a renal lesion in several aspects, including tuberous sclerosis complex association and immunoreactivity to both HMB-45 and MART-1 [29].

Regulatory relationships of MLANA

  • Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL-2 was able to promote the expansion of Melan-A/MART-1(27-35) tetramer positive cells [30].
  • In melanoma patients, Melan-A-specific T cells up-regulated 2B4 in parallel with in vivo differentiation [31].
  • In addition, some of the markers may identify patients likely to respond better to a new type of therapy (e.g., anti-angiogenic therapy in a patient whose tumor is overexpressing VEGF or immunotherapy for a patient whose tumor is expressing high levels of MART-1) [32].
  • To study the requirements for expansion of naive melan-A CTL from healthy donors, we set up an in vitro priming protocol and, using tetramer assays, we demonstrate that the activity and phenotype of the expanded melan-A CTL are profoundly influenced by the type of APC used [33].
  • However, these IL-10-grown DC can efficiently activate the epitope-specific CD8(+) T cells when they are made to present the epitope following transduction with an adenoviral vector expressing the MART-1 antigen [34].

Other interactions of MLANA

  • In recent years, it has become evident that T cells can recognize peptides of melanocytic lineage antigens such as gp100, MART-1, and tyrosinase at the tumor cell surface and can subsequently destroy these cells [20].
  • Additional samples of Melan-A/MART-1-positive, gp100-positive primary melanomas from six non-HLA-A2 patients and four autologous normal skin controls failed to reveal a TCRBV14 predominance in such tissues [1].
  • Finally, we demonstrate that brain metastasis-derived cell cultures significantly overexpress Melan-A and MAGE-3, compared to primary tumours and other metastatic sites (P-value range: 0.05-0.001) [35].
  • Our data show induction of CD8+ T cells specific for the melanosomal peptides MART-1/Melan-A(27-35) or tyrosinase(1-9), as well as IFN-gamma-releasing KLH-specific T cells, in two of six vaccinated melanoma patients, but do not support an association between the induction of these T cells and clinical responses [36].
  • Surprisingly, Mart-1 identified rare melanocytes in 67% of vitiligo cases and a significantly larger pool of melanocytes in LS and controls other than those labeled by Mel-5 [37].

Analytical, diagnostic and therapeutic context of MLANA


  1. Overexpression of the T-cell receptor beta-chain variable region TCRBV14 in HLA-A2-matched primary human melanomas. Salvi, S., Segalla, F., Rao, S., Arienti, F., Sartori, M., Bratina, G., Caronni, E., Anichini, A., Clemente, C., Parmiani, G. Cancer Res. (1995) [Pubmed]
  2. Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: evidence for immunoselection of antigen-loss variants in vivo. Jäger, E., Ringhoffer, M., Karbach, J., Arand, M., Oesch, F., Knuth, A. Int. J. Cancer (1996) [Pubmed]
  3. Expression of melanocyte-associated markers gp-100 and Melan-A/MART-1 in angiomyolipomas. An immunohistochemical and rt-PCR analysis. Jungbluth, A.A., Iversen, K., Coplan, K., Williamson, B., Chen, Y.T., Stockert, E., Old, L.J., Busam, K.J. Virchows Arch. (1999) [Pubmed]
  4. Immunohistochemical distinction of epithelioid histiocytic proliferations from epithelioid melanocytic nevi. Busam, K.J., Granter, S.R., Iversen, K., Jungbluth, A.A. The American Journal of dermatopathology. (2000) [Pubmed]
  5. Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi. Kucher, C., Zhang, P.J., Pasha, T., Elenitsas, R., Wu, H., Ming, M.E., Elder, D.E., Xu, X. The American Journal of dermatopathology. (2004) [Pubmed]
  6. Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers. Bioley, G., Jandus, C., Tuyaerts, S., Rimoldi, D., Kwok, W.W., Speiser, D.E., Tiercy, J.M., Thielemans, K., Cerottini, J.C., Romero, P. J. Immunol. (2006) [Pubmed]
  7. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Lee, P.P., Yee, C., Savage, P.A., Fong, L., Brockstedt, D., Weber, J.S., Johnson, D., Swetter, S., Thompson, J., Greenberg, P.D., Roederer, M., Davis, M.M. Nat. Med. (1999) [Pubmed]
  8. Thymic selection generates a large T cell pool recognizing a self-peptide in humans. Zippelius, A., Pittet, M.J., Batard, P., Rufer, N., de Smedt, M., Guillaume, P., Ellefsen, K., Valmori, D., Liénard, D., Plum, J., MacDonald, H.R., Speiser, D.E., Cerottini, J.C., Romero, P. J. Exp. Med. (2002) [Pubmed]
  9. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo. Yee, C., Thompson, J.A., Roche, P., Byrd, D.R., Lee, P.P., Piepkorn, M., Kenyon, K., Davis, M.M., Riddell, S.R., Greenberg, P.D. J. Exp. Med. (2000) [Pubmed]
  10. Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome. Romanini, A., Manca, G., Pellegrino, D., Murr, R., Sarti, S., Bianchi, F., Alsharif, A., Orlandini, C., Zucchi, V., Castagna, M., Gandini, D., Salimbeni, G., Ghiara, F., Barachini, P., Mariani, G. Ann. Oncol. (2005) [Pubmed]
  11. Analysis of melanoma cells in peripheral blood by reverse transcription-polymerase chain reaction for tyrosinase and MART-1 after mononuclear cell collection with cell preparation tubes: a comparison with the whole blood guanidinium isothiocyanate RNA isolation method. de Vries, T.J., Fourkour, A., Punt, C.J., Ruiter, D.J., van Muijen, G.N. Melanoma Res. (2000) [Pubmed]
  12. Prevention of an additional surgery for regional lymphadenectomy in melanoma: rapid intraoperative immunostaining of sentinel lymph node imprint smears. Shidham, V.B., Komorowski, R., Neuberg, M., Walker, A., Campbell, B.H., Chang, C.C., Dzwierzynski, W.W. Diagnostic pathology [electronic resource]. (2006) [Pubmed]
  13. Diagnostic utility of the monoclonal antibody A103 in fine-needle aspiration biopsies of the adrenal. Shin, S.J., Hoda, R.S., Ying, L., DeLellis, R.A. Am. J. Clin. Pathol. (2000) [Pubmed]
  14. Evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma: higher diagnostic accuracy with Melan-A and MART-1 compared with S-100 protein and HMB-45. Shidham, V.B., Qi, D.Y., Acker, S., Kampalath, B., Chang, C.C., George, V., Komorowski, R. Am. J. Surg. Pathol. (2001) [Pubmed]
  15. Immunogenicity without immunoselection: a mutant but functional antioxidant enzyme retained in a human metastatic melanoma and targeted by CD8(+) T cells with a memory phenotype. Sensi, M., Nicolini, G., Zanon, M., Colombo, C., Molla, A., Bersani, I., Lupetti, R., Parmiani, G., Anichini, A. Cancer Res. (2005) [Pubmed]
  16. Uveal and cutaneous melanoma: shared expression characteristics of melanoma-associated antigens. van Dinten, L.C., Pul, N., van Nieuwpoort, A.F., Out, C.J., Jager, M.J., van den Elsen, P.J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  17. Newly established clear cell sarcoma (malignant melanoma of soft parts) cell line expressing melanoma-associated Melan-A antigen and overexpressing C-MYC oncogene. Moritake, H., Sugimoto, T., Asada, Y., Yoshida, M.A., Maehara, Y., Epstein, A.L., Kuroda, H. Cancer Genet. Cytogenet. (2002) [Pubmed]
  18. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. Rosenberg, S.A., Zhai, Y., Yang, J.C., Schwartzentruber, D.J., Hwu, P., Marincola, F.M., Topalian, S.L., Restifo, N.P., Seipp, C.A., Einhorn, J.H., Roberts, B., White, D.E. J. Natl. Cancer Inst. (1998) [Pubmed]
  19. Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma. Miller, A.J., Du, J., Rowan, S., Hershey, C.L., Widlund, H.R., Fisher, D.E. Cancer Res. (2004) [Pubmed]
  20. Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions. de Vries, T.J., Fourkour, A., Wobbes, T., Verkroost, G., Ruiter, D.J., van Muijen, G.N. Cancer Res. (1997) [Pubmed]
  21. Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. Kawakami, Y., Eliyahu, S., Jennings, C., Sakaguchi, K., Kang, X., Southwood, S., Robbins, P.F., Sette, A., Appella, E., Rosenberg, S.A. J. Immunol. (1995) [Pubmed]
  22. MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes. Hoashi, T., Watabe, H., Muller, J., Yamaguchi, Y., Vieira, W.D., Hearing, V.J. J. Biol. Chem. (2005) [Pubmed]
  23. Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma. Clemons-Miller, A.R., Chatta, G.S., Hutchins, L., Angtuaco, E.J., Ravaggi, A., Santin, A.D., Cannon, M.J. Clin. Cancer Res. (2001) [Pubmed]
  24. Immunohistochemical study of melanocytic differentiation antigens in cutaneous malignant melanoma. A comparison of six commercial antibodies and one non-commercial antibody in nodular melanoma, superficially spreading melanoma and lentigo maligna melanoma. Kocan, P., Jurkovic, I., Böör, A., Dudríková, K., Krajcár, R., Benický, M., Kromydaki, A. Ceskoslovenská patologie. (2004) [Pubmed]
  25. Cell fusion: an approach to generating constitutively proliferating human tumor antigen-presenting cells. Jantscheff, P., Spagnoli, G., Zajac, P., Rochlitz, C.F. Cancer Immunol. Immunother. (2002) [Pubmed]
  26. Primary malignant melanoma of the oral cavity: a case report. López Ortega, K., Soares de Araújo, N., Bitu de Souza, F., Magalhães, M.H. International journal of dermatology. (2004) [Pubmed]
  27. Survival and tumor localization of adoptively transferred Melan-A-specific T cells in melanoma patients. Meidenbauer, N., Marienhagen, J., Laumer, M., Vogl, S., Heymann, J., Andreesen, R., Mackensen, A. J. Immunol. (2003) [Pubmed]
  28. Subcellular localization of the melanoma-associated protein Melan-AMART-1 influences the processing of its HLA-A2-restricted epitope. Rimoldi, D., Muehlethaler, K., Salvi, S., Valmori, D., Romero, P., Cerottini, J.C., Levy, F. J. Biol. Chem. (2001) [Pubmed]
  29. Cutaneous angiolipoleiomyoma. Makino, E., Yamada, J., Tada, J., Arata, J., Iwatsuki, K. J. Am. Acad. Dermatol. (2006) [Pubmed]
  30. Selective responsiveness to common gamma chain cytokines in peripheral blood-derived cytotoxic T lymphocytes induced by Melan-A/MART-1(27-35)targeted active specific immunotherapy. von Holzen, U., Adamina, M., Bolli, M., Weber, W.P., Zajac, P., Groeper, C., Reschner, A., Feder, C., Schumacher, R., Marti, W., Oertli, D., Heberer, M., Spagnoli, G.C. Int. J. Cancer (2005) [Pubmed]
  31. The activatory receptor 2B4 is expressed in vivo by human CD8+ effector alpha beta T cells. Speiser, D.E., Colonna, M., Ayyoub, M., Cella, M., Pittet, M.J., Batard, P., Valmori, D., Guillaume, P., Liénard, D., Cerottini, J.C., Romero, P. J. Immunol. (2001) [Pubmed]
  32. Update of diagnostic and prognostic markers in cutaneous malignant melanoma. Reed, J.A., Albino, A.P. Dermatologic clinics. (1999) [Pubmed]
  33. Mature dendritic cells prime functionally superior melan-A-specific CD8+ lymphocytes as compared with nonprofessional APC. Salio, M., Shepherd, D., Dunbar, P.R., Palmowski, M., Murphy, K., Wu, L., Cerundolo, V. J. Immunol. (2001) [Pubmed]
  34. Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocyte-derived dendritic cells. Mehrotra, S., Chhabra, A., Chakraborty, A., Chattopadhyay, S., Slowik, M., Stevens, R., Zengou, R., Mathias, C., Butterfield, L.H., Dorsky, D.I., Economou, J.S., Mukherji, B., Chakraborty, N.G. Immunology (2004) [Pubmed]
  35. Expression of melanoma-associated antigens in melanoma cell cultures. Urosevic, M., Braun, B., Willers, J., Burg, G., Dummer, R. Exp. Dermatol. (2005) [Pubmed]
  36. Analysis of T-cell responses in metastatic melanoma patients vaccinated with dendritic cells pulsed with tumor lysates. Griffioen, M., Borghi, M., Schrier, P.I., Osanto, S., Schadendorf, D. Cancer Immunol. Immunother. (2004) [Pubmed]
  37. Possible mechanisms of hypopigmentation in lichen sclerosus. Carlson, J.A., Grabowski, R., Mu, X.C., Del Rosario, A., Malfetano, J., Slominski, A. The American Journal of dermatopathology. (2002) [Pubmed]
  38. Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens. Jäeger, E., Bernhard, H., Romero, P., Ringhoffer, M., Arand, M., Karbach, J., Ilsemann, C., Hagedorn, M., Knuth, A. Int. J. Cancer (1996) [Pubmed]
  39. Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients. Palermo, B., Campanelli, R., Mantovani, S., Lantelme, E., Manganoni, A.M., Carella, G., Da Prada, G., della Cuna, G.R., Romagne, F., Gauthier, L., Necker, A., Giachino, C. Eur. J. Immunol. (2001) [Pubmed]
  40. Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100. Skipper, J.C., Gulden, P.H., Hendrickson, R.C., Harthun, N., Caldwell, J.A., Shabanowitz, J., Engelhard, V.H., Hunt, D.F., Slingluff, C.L. Int. J. Cancer (1999) [Pubmed]
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