Expression of cell–cell interacting genes distinguishes hlxb9/tel from mll-positive childhood acute myeloid leukemia

Access through your institution Buy or subscribe Molecular characterization of leukemic cells is a continuously emerging field and has become fundamental for therapy stratification and

prediction of event-free survival (EFS). Infant acute myeloid leukemia (AML) is in >60% cases characterized by a genomic rearrangement involving the mixed lineage leukemia (_MLL_) locus

(11q23) and the expression of a fusion protein (>50 fusion partners are described). Patients with primary diagnosis of _MLL_-positive leukemia are young (<2 years) and have generally

an inferior outcome compared with _MLL_-negative patients.1 We and others recently described a separate cohort of _MLL_-negative infant AML characterized by an early disease onset (<2

years) as well as t(7;12) _HLXB9/TEL_ (=_MNX1/ETV6_) rearrangement and with concomitant high expression of _HLXB9_ (_MNX1_). Surprisingly, all patients relapsed having a 3-year EFS of 0%.2,

3 The role of HLXB9, a transcription factor of the family of homeobox proteins is rarely studied in hematopoiesis and the data regarding its ability to cause malignant transformation of

hematopoietic stem cells (HSCs) is not yet available. Interestingly, germline mutations of _HLXB9_ lead to annorectal malformations and Currarino syndrome in children, but hematopoietic

abnormalities are not described.4 The poor clinical outcome in this _HLXB9/TEL_-positive leukemia subset prompted us to comprehensively characterize the two entities of _MLL_- and

_HLXB9/TEL_-positive AML regarding their cellular morphology, transcriptional profile and transformation process. In view of the clinical and immunophenotypic similarities of the two

leukemia entities, such as young age at diagnosis, coexpression of myeloid and T-cell antigens and bad clinical outcome, we aimed to characterize the molecular footprint representing the two

leukemia entities. Gene expression profiles of _MLL_-positive acute lymphoblastic leukemia and AML are very well studied and a recent report described specific _MLL_-associated and

upregulated genes, such as _MEIS1_ and _HOX_ genes, in discrepancy to _MLL_-negative leukemia, using the Affymetrix platform (Affymetrix, Santa Clara, CA, USA).6 The most frequent and

differentially expressed _HOX_ genes in human _MLL_-positive leukemia are _HOXA5_ and _HOXA9_. MLL fusion proteins can induce transcription from the _HOXA9_ and _MEIS1_ locus and probably

promote transformation, extensively shown in murine transplantation models.1 In contrast, almost nothing is known about the gene expression pattern of t(7;12)-positive leukemia. This is a

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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Krivtsov AV, Armstrong SA . MLL

translocations, histone modifications and leukaemia stem-cell development. _Nat Rev Cancer_ 2007; 7: 823–833. Article  CAS  Google Scholar  * Hauer J, Tosi S, Schuster FR, Harbott J, Kolb

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Scholar  * von Bergh AR, van Drunen E, van Wering ER, van Zutven LJ, Hainmann I, Lönnerholm G _et al_. High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal

outcome and ectopic expression of HLXB9. _Genes Chromosomes Cancer_ 2006; 45: 731–739. Article  CAS  Google Scholar  * Currarino G, Coln D, Votteler T . Triad of anorectal, sacral, and

presacral anomalies. _Am J Roentgenol_ 1981; 137: 395–398. Article  CAS  Google Scholar  * Wada H, Masuda K, Satoh R, Kakugawa K, Ikawa T, Katsura Y _et al_. Adult T-cell progenitors retain

myeloid potential. _Nature_ 2008; 452: 768–772. Article  CAS  Google Scholar  * Zangrando A, Dell’orto MC, Te Kronnie G, Basso G . MLL rearrangements in pediatric acute lymphoblastic and

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niche regulates hematopoietic stem cells. _Chem Biol Interact_ 2010; 19: 7–15. Article  Google Scholar  Download references ACKNOWLEDGEMENTS We thank Dr Wöβmann, the University Childrens

Hospital, Giessen; Prof Dr Niemeyer, University Chidren's Hospital Freiburg; Prof Dr Holter, University Hospital Erlangen and Prof Dr Jürgens, University Hospital Münster for providing

clinical patient data and supporting this work. We also thank Dr Sabrina Tosi, Brunel University for fruitful discussions and collaboration. This work was supported by research funds of the

Heinrich Heine University, Düsseldorf, Germany. AUTHOR INFORMATION Author notes * J Hauer and A Borkhardt: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS *

Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Düsseldorf, Germany S Wildenhain, F R Schuster, V

Binder, J Hauer & A Borkhardt * Department of Medical Informatics and Biomathematics, University of Münster, Münster, Germany C Ruckert * Department of Pediatric Hematology and Oncology,

Justus-Liebig-University, Giessen, Germany S Röttgers & J Harbott * Department of Hematology, Oncology and Tumor Immunology, HELIOS Clinic, Berlin-Buch, Germany W-D Ludwig * Laboratoire

d’hematologie, Hôpital Necker Enfants Malades, Paris, France K Beldjord * Department of Genetics, Friedrich-Alexander University, Erlangen, Germany R Slany Authors * S Wildenhain View

author publications You can also search for this author inPubMed Google Scholar * C Ruckert View author publications You can also search for this author inPubMed Google Scholar * S Röttgers

View author publications You can also search for this author inPubMed Google Scholar * J Harbott View author publications You can also search for this author inPubMed Google Scholar * W-D

Ludwig View author publications You can also search for this author inPubMed Google Scholar * F R Schuster View author publications You can also search for this author inPubMed Google

Scholar * K Beldjord View author publications You can also search for this author inPubMed Google Scholar * V Binder View author publications You can also search for this author inPubMed 

Google Scholar * R Slany View author publications You can also search for this author inPubMed Google Scholar * J Hauer View author publications You can also search for this author inPubMed 

Google Scholar * A Borkhardt View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to J Hauer. ETHICS DECLARATIONS

COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wildenhain, S., Ruckert, C., Röttgers,

S. _et al._ Expression of cell–cell interacting genes distinguishes HLXB9/TEL from MLL-positive childhood acute myeloid leukemia. _Leukemia_ 24, 1657–1660 (2010).

https://doi.org/10.1038/leu.2010.146 Download citation * Published: 01 July 2010 * Issue Date: September 2010 * DOI: https://doi.org/10.1038/leu.2010.146 SHARE THIS ARTICLE Anyone you share

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