Translocation t(5;14)(q35;q32) in three cases of childhood T cell acute lymphoblastic leukemia: a new recurring and cryptic abnormality

Hélias, Catherine; Leymarie, Vincent; Entz‐Werlé, Natacha; Falkenrodt, A.; Eyer, Didier; Costa, J Aurich; Cherif, Dorra; Lutz, Patrick; Lessard, Michel

doi:10.1038/sj.leu.2402347

Cited by 26 publications

(19 citation statements)

References 16 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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Adult T-cell acute lymphoblastic leukemia (T-ALL) continues to represent an unfavorable disease. Molecularly based treatment stratifications could help improve outcome. The prognostic impact of HOX11 and HOX11L2 expression has been an area of controversy. We have investigated 286 adult T-ALL patients enrolled into the German Multicenter ALL (GMALL) therapy protocols by comparative real-time RT-PCR. High HOX11 expression and HOX11L2 expression were predominantly seen in thymic T-ALL (P ¼ 0.031). In a multivariate analysis HOX11L2 expression proved to be an independent adverse risk factor for relapse-free survival (RFS) with a hazard ratio (HR) of 2.02 (P ¼ 0.023) and an HR for overall survival (OS) of 1.81 (P ¼ 0.021), both adjusted for the immunophenotype. HOX11 expression was found to have a favorable impact on RFS (HR 0.51; P ¼ 0.048) but did not exhibit a significant impact on OS. A subgroup analysis for thymic T-ALL revealed a more pronounced negative correlation of HOX11L2 expression with RFS (HR 3.26; P ¼ 0.002) and OS (HR 2.38; P ¼ 0.009). Although the prognostic impact of HOX11 in T-ALL is less clear, HOX11L2 expression identifies a small subset of high-risk patients, who are so far classified as standard-risk group. Thus, patients with aberrant HOX11L2 expression should be considered early as candidates for intensified treatment regimes.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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“…10,11 In the majority of T-ALL patients carrying this translocation, the breakpoints on band 5q35 are clustered within or downstream of the RANBP17 gene. This translocation does not result in deregulation of RANBP17, but in overexpression of the TLX3 (HOX11L2) gene that is located downstream (telomeric) of RANBP17.…”

Section: Translocations Involving the Ranbp17 And Tlx3 (Hox11l2) Regimentioning

confidence: 99%

“…[5][6][7][8][9] Recently, a new recurrent, but cryptic translocation t(5;14)(q35;q32) has been described in T-ALL. 10,11 In the majority of patients with this translocation, the breakpoint is located within or downstream of the RANBP17 gene at 5q35; the breakpoints at 14q32 are very heterogeneous. This translocation results in overexpression of the TLX3 (HOX11L2) gene, which is located downstream of RANBP17.…”

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confidence: 99%

Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

Burg

Poulsen²,

Hunger

et al. 2004

Leukemia

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Chromosome aberrations are frequently observed in precursor-B-acute lymphoblastic leukemias (ALL) and T-cell acute lymphoblastic leukemias (T-ALL). These translocations can form leukemia-specific chimeric fusion proteins or they can deregulate expression of an (onco)gene, resulting in aberrant expression or overexpression. Detection of chromosome aberrations is an important tool for risk classification. We developed rapid and sensitive split-signal fluorescent in situ hybridization (FISH) assays for six of the most frequent chromosome aberrations in precursor-B-ALL and T-ALL. The split-signal FISH approach uses two differentially labeled probes, located in one gene at opposite sites of the breakpoint region. Probe sets were developed for the genes TCF3 (E2A) at 19p13, MLL at 11q23, ETV6 at 12p13, BCR at 22q11, SIL-TAL1 at 1q32 and TLX3 (HOX11L2) at 5q35. In normal karyotypes, two colocalized green/red signals are visible, but a translocation results in a split of one of the colocalized signals. Split-signal FISH has three main advantages over the classical fusionsignal FISH approach, which uses two labeled probes located in two genes. First, the detection of a chromosome aberration is independent of the involved partner gene. Second, split-signal FISH allows the identification of the partner gene or chromosome region if metaphase spreads are present, and finally it reduces false-positivity. Leukemia ( Chromosome aberrations play an important role in hematological malignancies. 1 In ALL, most of these aberrations concern balanced translocations involving genes that play key roles in the development and function of lymphoid cells, such as transcription factors, cell cycle regulators, and signal transduction molecules. Balanced translocations can result in fusion of two genes that encode leukemia-specific chimeric (fusion) proteins. The fusion proteins have functional features that differ from the corresponding wild-type proteins and mostly play a role in leukemogenesis. In addition to the new features of the fusion protein, loss of wild-type activity due to the translocation (in some translocations enhanced by deletion of the second allele) might contribute to oncogenesis. Alternatively, chromosome translocations can result in deregulated expression of (onco)genes as a direct consequence of a translocation to a regulatory element, for example, an immunoglobulin (Ig) or T-cell receptor (TCR) enhancer. 2,3 The most frequent translocations in precursor-B-ALL are t(1;19)(q23;p13) t(4;11)(q21;q23), t(12;21)(p13;q22), and t(9;22)(q34;q11), all four of which result in generation of fusion genes. The t(1;19)(q23;p13) fuses the transcription factorencoding gene TCF3 (E2A) with the transcription factor PBX1. In t(4;11)(q21;q23), the MLL gene at 11q23, which encodes a putative DNA-binding protein, is translocated to the MLLT2 (AF4) gene. The MLL gene is involved in many other translocations in ALL and acute myeloid leukemia (AML). Until now, more than 30 partner genes have been identified. 4 The t(12;21)(p13;q22) involves th...

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“…IPM-FISH (IRS-PCR Multiplex FISH) was used in one laboratory. 4 Occasionally, IGH BAC probe 158A2 (H. AvetLoiseau, Nantes) was also used.…”

Section: Cytogenetic and Fish Studiesmentioning

confidence: 99%

“…2 More recently, the translocation t(5;14)(q35;q32), only observed upon FISH analyses, was reported in approximately 20% of childhood T-cell ALLs. 3,4 On chromosome 14, the breakpoints are scattered in the vicinity of the CTIP2/BCL11B gene, which is highly expressed during T-cell lymphoid differentiation. On chromosome 5, the t(5;14)(q35;q14) usually disrupts the RANBP17 gene, but is described to result in the ectopic transcriptional activation of HOX11L2, a gene encoding a homeobox transcription factor of the HOX11 family.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2003

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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.

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Translocation t(5;14)(q35;q32) in three cases of childhood T cell acute lymphoblastic leukemia: a new recurring and cryptic abnormality

Cited by 26 publications

References 16 publications

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

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

Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

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

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