Adult T-cell leukemia

Definition:

Adult T-cell leukemia (ATL) is one of the most aggressive hematologic malignancies and is caused by human T-cell leukemia virus type 1 (HTLV-1). The HTLV-1 Tax protein has been demonstrated to be the oncogenic protein of the virus. Tax may contribute to the process of carcinogenesis by a variety of mechanisms, including upregulating the expression of cellular genes involved in T cell growth and proliferation, including IL-2, IL-2R-alpha, and IL-15. However, ATL cells do not always need Tax expression in the later stage of leukemogenesis. Genetic and epigenetic changes should be implicated in such multistep leukemogenesis. Regarding genetic changes, mutation of p53, and deletion of p16 have been reported in ATL. Mutations of Fas gene are also reported in patients with ATL cells. However, such genetic changes were not frequently detected. In this regard, epigenetic change of p16/INK4A gene was more frequent in ATL cells, and accumulated according to the disease progression. This finding suggests that epigenetic change, including DNA methylation, plays an important role in the leukemogenesis of ATL.

References:

[1]. Jun-ichirou Yasunaga, et al. Human T-cell leukemia virus type I induces adult T-cell leukemia: from clinical aspects to molecular mechanisms. Cancer Control. 2007 Apr;14(2):133-40. [Content Brief]

[2]. Jun-ichirou Yasunaga, et al. Leukemogenesis of adult T-cell leukemia. Int J Hematol. 2003 Nov;78(4):312-20. [Content Brief]

[3]. Masao Matsuoka, et al. Human T-cell leukemia virus type I and adult T-cell leukemia. Oncogene. 2003 Aug 11;22(33):5131-40. [Content Brief]

[4]. Ruth F Jarrett, et al. Viruses and lymphoma/leukaemia. J Pathol. 2006 Jan;208(2):176-86. [Content Brief]

[5]. T Maeda, et al. Fas gene mutation in the progression of adult T cell leukemia. J Exp Med. 1999 Apr 5;189(7):1063-71. [Content Brief]

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