Abstract：
:Human T cell leukemias can arise from oncogenes activated by specific chromosomal translocations involving the T cell receptor genes. Here we show that five different T cell oncogenes (HOX11, TAL1, LYL1, LMO1, and LMO2) are often aberrantly expressed in the absence of chromosomal abnormalities. Using oligonucleotide microarrays, we identified several gene expression signatures that were indicative of leukemic arrest at specific stages of normal thymocyte development: LYL1+ signature (pro-T), HOX11+ (early cortical thymocyte), and TAL1+ (late cortical thymocyte). Hierarchical clustering analysis of gene expression signatures grouped samples according to their shared oncogenic pathways and identified HOX11L2 activation as a novel event in T cell leukemogenesis. These findings have clinical importance, since HOX11 activation is significantly associated with a favorable prognosis, while expression of TAL1, LYL1, or, surprisingly, HOX11L2 confers a much worse response to treatment. Our results illustrate the power of gene expression profiles to elucidate transformation pathways relevant to human leukemia.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Ferrando AA,Neuberg DS,Staunton J,Loh ML,Huard C,Raimondi SC,Behm FG,Pui CH,Downing JR,Gilliland DG,Lander ES,Golub TR,Look ATdoi
10.1016/s1535-6108(02)00018-1keywords:
subject
Has Abstractpub_date
2002-02-01 00:00:00pages
75-87issue
1eissn
1535-6108issn
1878-3686pii
S1535610802000181journal_volume
1pub_type
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