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The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia

2006; Elsevier BV; Volume: 108; Issue: 10 Linguagem: Inglês

10.1182/blood-2006-04-019927

1528-0020

Pieter Van Vlierberghe, Martine van Grotel, H. Berna Beverloo, Charles Lee, Thorunn Helgason, Jessica G. C. A. M. Buijs-Gladdines, Monique Passier, E R van Wering, A. Veerman, W. A. Kamps, Jules P.P. Meijerink, R. Pieters,

Chronic Myeloid Leukemia Treatments

To identify new cytogenetic abnormalities associated with leukemogenesis or disease outcome, T-cell acute lymphoblastic leukemia (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 (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 of 6 del(11)(p12p13)-positive T-ALL patients, in the same manner as in 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 until now.