t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH)

Abstract

To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Franç ais de Cytogé né tique Hé matologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children p15 years and 153 adults), and 67 (18.5%) [47 children (22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5;14)q35;q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly higher in positive than in negative children. Out of the 63 positive patients investigated by conventional cytogenetics, 32 exhibited normal karyotype, whereas the others 31 showed clonal chromosome abnormalities, which did not include classical T-ALL specific translocations. Involvement of the RANBP17/HOX11L2 locus was ascertained by fluorescence in situ hybridization in six variant or alternative (three-way translocation or cytogenetic partner other than 14q32) translocations out of the 223 patients. Our results also show that HOX11L2 expression essentially occurs as a result of a 5q35 rearrangement, but is not associated with another identified T-ALL specific recurrent genetic abnormality, such as SIL-TAL fusion or HOX11 expression.

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

“…4 This study also includes 229 patients studied in the HOX11L2 study of the GFCH. 16 Incidence and immunophenotypical and molecular features of TCRb-HOXA rearranged T-ALL…”

“…The only inclusion criterion was the diagnosis of T-ALL and the availability of fixed cells for FISH (n ¼ 424) and/or RNA or frozen cells for real-time quantitative RT-PCR (n ¼ 170 of 424). Besides newly diagnosed T-ALLs, these series of patient samples includes 229 cases analyzed in the HOX11L2 study of the Groupe Francophone de Cytogénétique Hématologique (GFCH), 16 patients analyzed in the first study, 3 that is, 94 patients analyzed with FISH and 26 with real-time quantitative PCR, and patients of another study, 4 that is, 92 patients analyzed by FISH and 21 with real-time quantitative PCR. This total series of patients included 50% children and adults.…”

NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance

“…1 In rare APL cases, variant chromosome translocations have been reported, which fuse RARa gene with partner genes other than PML, such as t(11;17)(q23;q21), 2 t(5;17)(q35;q21), 3 t(11;17)(q13;q21) and dup(17)(q21.3;q23). 2 In these cases RARa is fused to the PLZF, NPM, NuMA and STAT5b genes, respectively. Patients with fusion genes involving NPM and NuMA appear to be sensitive to ATRA, like patients with PML-RARa rearrangement.…”

“…1,2 The prognostic significance of the genetic abnormality in patients with this subtype of ALL is still controversial, claimed as unfavorable for some groups 3,4 or regarded as neutral for others. 5,6 Recently, episomal amplification encompassing the ABL1 gene has been found in 2.3 and 4.3% of childhood and adult T-ALL.…”

Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization

“…The development of fluorescence in situ hybridization (FISH) has expanded the utility of cytogenetics. It has identified a number of clinically relevant chromosomal abnormalities (Romana et al, 1994;Berger et al, 2003), and allowed the detection of these alterations in patients with failed cytogenetic results, normal, complex or illdefined karyotypes (Harrison et al, 2005). In spite of its limited resolution, chromosome-based comparative genomic hybridization (cCGH) (Kallioniemi et al, 1992) has provided additional genomic information in some groups of patients (Haas et al, 1998;Larramendy et al, 1998).…”