T-cell acute lymphoblastic leukemia

Definition:

Acute lymphocytic leukemia (ALL) is a clonal stem cell malignancy of excessive lymphoblast proliferation. It is now understood that ALL and lymphoblastic lymphoma are the same disease entities at the morphologic and immunophenotypic levels and classified as either B- and T-cell lymphoblastic leukemia/lymphoma (B-ALL and T-ALL). T-ALL comprises 15% of paediatric and 25% of adult ALL cases. T cell transformation is a multi-step process in which different genetic alterations cooperate to alter the normal mechanisms that control cell growth, proliferation, survival, and differentiation during thymocyte development. In this context, constitutive activation of NOTCH1 signaling is the most prominent oncogenic pathway in T cell transformation. In addition, T-ALLs characteristically show the translocation and aberrant expression of transcription factor oncogenes. These oncogenic transcription factors include T-cell leukaemia homeobox protein 1 (TLX1 also known as HOX11), TLX3 (HOX11L2), LYL1, TAL1 and MLL.

References:

[1]. Daniel A Arber, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. [Content Brief]

[2]. Kathryn G Roberts, et al. Genomics in acute lymphoblastic leukaemia: insights and treatment implications. Nat Rev Clin Oncol. 2015 Jun;12(6):344-57. [Content Brief]

[3]. Michael A Teitell, et al. Molecular genetics of acute lymphoblastic leukemia. Annu Rev Pathol. 2009;4:175-98. [Content Brief]

[4]. Monika D Kraszewska, et al. T-cell acute lymphoblastic leukaemia: recent molecular biology findings. Br J Haematol. 2012 Feb;156(3):303-15. [Content Brief]

[5]. Pieter Van Vlierberghe, et al. The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest. 2012 Oct;122(10):3398-406. [Content Brief]

[6]. Robert Frank Cornell, et al. Adult acute leukemia. Dis Mon. 2012 Apr;58(4):219-38. [Content Brief]

[7]. Y Xia, et al. TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11416-20. [Content Brief]

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