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Elevated TRIB 2 with NOTCH 1 activation in paediatric/adult T ‐ ALL
Author(s) -
Han Maura M.,
Lohan Fiona,
Erbilgin Yucel,
Sayitoglu Muge,
O'Hagan Kathleen,
Mills Ken,
Ozbek Ugur,
Keeshan Karen
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09222.x
Subject(s) - chemistry , microbiology and biotechnology , biology
Summary TRIB 2 is a potent oncogene, elevated in a subset of human acute myeloid leukaemias ( AML ) with a mixed myeloid/lymphoid phenotype and NOTCH 1 mutations. Although rare in AML , activating NOTCH 1 mutations occur in 50% of all T cell acute lymphoblastic leukaemias ( T ‐ ALL ). TRIB 2 is a NOTCH 1 target gene that functions in the degradation of key proteins and modulation of MAPK signalling pathways, implicated in haematopoietic cell survival and proliferation. This study showed that TRIB 2 expression level is highest in the lymphoid compartment of normal haematopoietic cells, specifically in T cells. Analysis of TRIB 2 expression across 16 different subtypes of human leukaemia demonstrated that TRIB 2 expression was higher in ALL phenotypes versus all other phenotypes including AML , chronic lymphocytic leukaemia (CLL), myelodysplastic syndrome (MDS) and chronic myeloid leukaemia (CML). A T cell profile was distinguished by high TRIB 2 expression in normal and malignant haematopoiesis. High TRIB 2 expression was seen in T ‐ ALL with normal karyotype and correlated with NOTCH signalling pathways. High TRIB 2 expression correlated with NOTCH 1/ FBXW 7 mutations in a paediatric T ‐ ALL cohort, strongly linking NOTCH 1 activation and high TRIB 2 expression in paediatric T ‐ ALL . The relationship between TRIB 2 and T cell signalling pathways uniquely identifies leukaemia subtypes and will be useful in the advancement of our understanding of T cell and ALL biology.