Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951

Abstract

In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n ‫؍‬ 35), 7% (n ‫؍‬ 10), and 12% (n ‫؍‬ 17), respectively. HOX11L2/ t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy.

Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group

“…The present analysis of HOX11 and HOX11L2 expression in 286 well-characterized and homogenously treated adult T-ALL patients does confirm and extend previous reports on a negative prognostic impact of HOX11L2 and a positive impact of HOX11 expression. [6][7][8]10 In addition, our analyses provides first evidence that the thymic T-ALL subtype can be further divided in a standard-risk and a high-risk subgroup.…”

“…An aberrant expression of this proto-oncogene was first found in patients with the translocations t(5;14)(q35;q32) and t(5;7)(q35;q21) as well as a t(5;14)(q33;q11). 8,15,16 HOX11L2 expression is described as the most common genetic finding in pediatric T-ALL with a frequency of approximately 23%. In adolescents it has been found in around 16% and is further declining to 11% in T-ALL patients older than 20 years.…”

“…Most studies to date have grouped low-expression samples together with samples not expressing HOX11. 8,9 Fluorescence-activated cell sorting analyses at the time of diagnosis revealed blast counts of 50% or higher in all samples. As a maximum input variation by a factor of two does not sufficiently explain the observed 2-3 log variation in HOX11 expression, we have differentiated between high, low and negative expression.…”

“…As previously indicated, HOX11 expression is found at both high and low levels. [6][7][8][9] The impact of low HOX11 expression has not yet been separately analyzed in adult T-ALL patients. Most studies to date have grouped low-expression samples together with samples not expressing HOX11.…”

“…6 However, available data are controversial regarding the clinical impact of aberrant HOX11 and HOX11L2 expression in childhood T-ALL, and few data are available in adult patients. [7][8][9][10] The pediatric and adult population might differ substantially in the activation status of these oncogenes. Also, little is known about a correlation of molecular data and the immunologic subtypes as an already established prognostic factor.…”