Hoxa cluster deregulation in t-all associated with both a tcrd-hoxa and a calm-af10 chromosomal translocation

Access through your institution Buy or subscribe Recognized T-cell acute lymphoblastic leukemias (T-ALLs) oncogenic pathways include transcriptional deregulation of oncogenes by

juxtapositioning to the T-cell receptor _β_ (_TCRB_) or _α/δ_ (_TCRA/D_) enhancer loci, resulting in overexpression of genes such as _LMO2_, _LMO1_, _LYL1_, _TAL1/SCL_, and homeodomain genes

such as _TLX1_/_HOX11_, _TLX3_/_HOX11L2_ or _HOXA_. A V(D)J error-type mechanism has been proposed to explain such recurrent chromosomal events but other processes are likely to intervene,

particularly those mediating the chromosomal break at the locus bearing the proto-oncogene.1 Evidence in favor of V(D)J-mediated errors include the presence of non-templated nucleotides

(n-diversity) at the chromosomal junction and of recognition signal sequences (RSS) or RSS-like sequences at the vicinity of the breakpoints on the derivative chromosomes, although putative

RSS-like sequences are usually incomplete. The _HOXA_ gene cluster on chromosome 7p15 has recently been described as a new recurrent _TCRB_ partner in T-ALL.2, 3 In cases with _TCRB-HOXA_

translocation, a variable but consistent combination of individual _HOXA_ genes on both sides of the breakpoint appears to be upregulated. The juxtapositioning of _TCRB_ enhancer elements

and the _HOXA_ locus disruption in itself might deregulate the whole cluster expression. In other cases, _trans_-regulating factors can deregulate the whole _HOXA_ cluster. The MLL protein

directly regulates _HOX_ family genes4 and chimeric MLL oncoproteins are recognized to mediate _HOX_ deregulation in AML and B- and T-lineage ALL.5 T-cell acute lymphoblastic leukemia with

_CALM-AF10_ fusions also demonstrate _HOXA_ cluster upregulation,2, 6 but the mechanisms mediating gene deregulation in these cases remain to be explored. This is a preview of subscription

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Marculescu R, Le T, Simon P, Jaeger U, Nadel B . V(D)J-mediated

translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. _J Exp Med_ 2002; 195: 85–98. Article  CAS  Google Scholar  * Soulier J, Clappier E,

Cayuela JM, Regnault A, Garcia-Peydro M, Dombret H _et al_. HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). _Blood_ 2005; 106: 274–286

[E-pub 2005 Mar 17]. Article  CAS  Google Scholar  * Speleman F, Cauwelier B, Dastugue N, Cools J, Verhasselt B, Poppe B _et al_. A new recurrent inversion, inv(7)(p15q34), leads to

transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. _Leukemia_ 2005; 19: 358–366. Article  CAS  Google Scholar  * Milne TA, Briggs SD, Brock

HW, Martin ME, Gibbs D, Allis CD _et al_. MLL targets SET domain methyltransferase activity to Hox gene promoters. _Mol Cell_ 2002; 10: 1107–1117. Article  CAS  Google Scholar  * Armstrong

SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD _et al_. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. _Nat Genet_

2002; 30: 41–47 [E-pub 2001 Dec 3]. Article  CAS  Google Scholar  * Dik WA, Brahim W, Braun C, Asnafi V, Dastugue N, Bernard OA _et al_. CALM-AF10+ T-ALL expression profiles are

characterized by overexpression of HOXA and BMI1 oncogenes. _Leukemia_ 2005; 19: 1948–1957. Article  CAS  Google Scholar  * Asnafi V, Radford-Weiss I, Dastugue N, Bayle C, Leboeuf D, Charrin

C _et al_. CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCR{gamma}{delta} lineage. _Blood_ 2003; 102: 1000–1006. Article  CAS  Google Scholar  * Asnafi V,

Beldjord K, Libura M, Villarese P, Millien C, Ballerini P _et al_. Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy.

_Blood_ 2004; 104: 4173–4180 [E-pub 2004 Mar 30]. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by the Fondation contre la leucémie de la

Fondation de France and Association de Recherche sur le Cancer (ARC). AUTHOR INFORMATION Author notes * J Bergeron: J Bergeron is a Research Fellow of The Terry Fox Foundation through an

award from the Natianal Cancer Institute of Canada AUTHORS AND AFFILIATIONS * Laboratoire d'Hématologie and INSERM EMI0210, Hôpital Necker-Enfants Malades, Université Paris-Descartes,

AP-HP, Paris, France J Bergeron, C Millien, E Delabesse, K Beldjord, E Macintyre & V Asnafi * Hematology Laboratory and INSERM U728, Institut Universitaire d'Hématologie, Hôpital

Saint-Louis and Paris 7 University, Paris, France E Clappier & J Soulier * Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium B Cauwelier & F Speleman *

Laboratoire d'Hématologie, Hôpital Purpan, Toulouse, France N Dastugue Authors * J Bergeron View author publications You can also search for this author inPubMed Google Scholar * E

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this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bergeron, J., Clappier, E., Cauwelier, B. _et al._ _HOXA_ cluster

deregulation in T-ALL associated with both a _TCRD-HOXA_ and a _CALM-AF10_ chromosomal translocation. _Leukemia_ 20, 1184–1187 (2006). https://doi.org/10.1038/sj.leu.2404187 Download

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