The Cryptic Chromosomal Deletion, del(11)(p12p13), as a New Activation Mechanism of LMO2 in Pediatric T-Cell Acute Lymphoblastic Leukemia.

To identify new cytogenetic abnormalities associated with leukemogenesis or disease outcome, T-ALL patient samples were analyzed by means of the array-comparative genome hybridization technique (array-CGH). Here, we report the identification of a new recurrent and cryptic deletion on chromosome 11, i.e. the del(11)(p12p13), in about 4% (6/138) of pediatric T-ALL patients. Detailed molecular-cytogenetic analysis revealed that this deletion activates the LMO2 oncogene in 4 out of 6 del(11)(p12p13) positive T-ALL patients, alike patients with an LMO2 translocation (9/138). The LMO2 activation mechanism of this deletion is loss of a negative regulatory region upstream of LMO2, causing activation of the proximal LMO2 promoter. LMO2 rearrangements, including this del(11)(p12p13) and t(11;14)(p13;q11) or t(7;11)(q35;p13), were found in the absence of other recurrent cytogenetic abnormalities involving HOX11L2, HOX11, CALM-AF10, TAL1, MLL or MYC. LMO2 abnormalities, represent about 9% (13/138) of pediatric T-ALL cases, and are more frequent in pediatric T-ALL than appreciated up till now.