HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis

Abstract

The most frequent oncogenic activation events characterized in childhood T acute lymphoblastic leukemia (T-ALL) result in the transcriptional activation of genes coding for transcription factors. The main genes are TAL1/SCL, a member of the basic region helix-loop-helix gene family, and HOX11L2, a member of the homeobox-containing protein family. To gain insight into the pathogenesis of this type of hematologic malignancy, we analyzed 28 T-ALL samples. SIL-TAL1/SCL fusion was detected in 6 patients; expression of HOX11L2 was observed in 6 patients and of HOX11 in 3 patients. With one exception, these activations did not occur simultaneously in the same patients, and they allowed the subclassification of 50% of the patients. SIL-TAL1 fusion was detected in association with HOX11 expression in one patient and with a t(8;14) (q24;q11) in another. High expression of LYL1, LMO2, or TAL1 was observed mainly in samples negative for HOX11L2 expression. HOX11L1 and HOX11 expression were observed in one instance each, in the absence of detectable chromosomal abnormality of their respective loci, on chromosomes 2 and 10, respectively. HOX11L2 expression was associated with a chromosome 5q abnormality, the location of the HOX11L2 locus in each case tested. Finally, our data show that HOX11L2 expression was a suitable marker for minimal residual disease follow-up and was significantly associated with relapse (P ‫؍‬ .02). (Blood. 2002;100:991-997)

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

“…[8][9][10]18,19 Reports on the FRALLE protocol with 6 HOX11L2-positive of 28 patients and the Total Therapy studies XI-XIII with 6 HOX11L2-positive of 59 patients revealed a negative prognostic impact of HOX11L2 expression. 6,7 Confirmed were these reports by an …”

“…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.…”

“…Furthermore, we observed an association of HOX11L2 (P ¼ 0.031) and HOX11 (Po0.0005) with the cortical immunophenotype, which has been reported previously. [6][7][8] Cave et al 8 interpreted the high proportion of HOX11L2-positive T-ALL cases with a cortical immunophenoytpe in their study as an indirect argument against a negative impact of HOX11L2 expression. In contrast, we propose that HOX11L2 expression identifies a subgroup of cortical T-ALL with an inferior outcome compared to the majority of cortical T-ALL patients.…”

“…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.…”