User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCR beta-HOXA rearrangement: a study of the Groupe Francophone de Cytogenetique Hematologique

Primary tabs

Cauwelier, B. Lefebvre, Christine Leroux, Dominique Poirel, Héléne [UCL] Graux, Carlos [UCL] Hagemeijer, Anne [KUL]

Recently, we and others described a new chromosomal rearrangement, that is, inv( 7)( p15q34) and t( 7; 7)( p15; q34) involving the T-cell receptor beta ( TCR beta) ( 7q34) and the HOXA gene locus ( 7p15) in 5% of T-cell acute lymphoblastic leukemia ( T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCR beta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients ( 3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCR beta-HOXA rearrangement ( 8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCR beta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCR beta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL ( SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRb- HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCR beta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2007
Language Anglais
Journal information "Leukemia" - Vol. 21, no. 1, p. 121-8 (2007)
Peer reviewed yes
Publisher Nature Publishing Group (London)
issn 0887-6924
e-issn 1476-5551
Publication status Publié
Affiliations UCL - MD/MINT - Département de médecine interne
UCL - (MGD) Service d'hématologie
UCL - (SLuc) Centre de génétique médicale UCL
MESH Subject Translocation, Genetic ; Transcriptional Activation ; Receptors, Antigen, T-Cell, alpha-beta - genetics ; Receptor, Notch1 - genetics ; Middle Aged ; Male ; Leukemia-Lymphoma, Adult T-Cell - genetics - pathology - physiopathology ; Immunophenotyping ; Humans ; Homeodomain Proteins - genetics ; Gene Rearrangement, T-Lymphocyte ; Female ; Chromosome Inversion ; Chromosome Deletion ; Child ; Adult ; Adolescent
Keywords TCR beta-HOXA rearrangement ; T-ALL ; HOXA10 ; HOXA10b
Links
  1. Pui Ching-Hon, Relling Mary V., Downing James R., Acute Lymphoblastic Leukemia, 10.1056/nejmra023001
  2. De Keersmaecker K, Haematologica, 90, 1116 (2005)
  3. Soulier J., HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL), 10.1182/blood-2004-10-3900
  4. Armstrong Scott A., Staunton Jane E., Silverman Lewis B., Pieters Rob, den Boer Monique L., Minden Mark D., Sallan Stephen E., Lander Eric S., Golub Todd R., Korsmeyer Stanley J., MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia, 10.1038/ng765
  5. Ferrando A. A., Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation, 10.1182/blood-2002-10-3221
  6. Dik W A, Brahim W, Braun C, Asnafi V, Dastugue N, Bernard O A, van Dongen J J M, Langerak A W, Macintyre E A, Delabesse E, CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes, 10.1038/sj.leu.2403891
  7. Asnafi V., CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCR   lineage, 10.1182/blood-2002-09-2913
  8. Yeoh Eng-Juh, Ross Mary E, Shurtleff Sheila A, Williams W.Kent, Patel Divyen, Mahfouz Rami, Behm Fred G, Raimondi Susana C, Relling Mary V, Patel Anami, Cheng Cheng, Campana Dario, Wilkins Dawn, Zhou Xiaodong, Li Jinyan, Liu Huiqing, Pui Ching-Hon, Evans William E, Naeve Clayton, Wong Limsoon, Downing James R, Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling, 10.1016/s1535-6108(02)00032-6
  9. Rozovskaia T, Feinstein E, Mor O, Foa R, Blechman J, Nakamura T, Croce C M, Cimino G, Canaani E, Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4 : 11) abnormality, 10.1038/sj.onc.1204174
  10. Ayton P. M., Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9, 10.1101/gad.1111603
  11. Milne Thomas A, Briggs Scott D, Brock Hugh W, Martin Mary Ellen, Gibbs Denise, Allis C.David, Hess Jay L, MLL Targets SET Domain Methyltransferase Activity to Hox Gene Promoters, 10.1016/s1097-2765(02)00741-4
  12. Nakamura Tatsuya, Mori Toshiki, Tada Shinichiro, Krajewski Wladyslaw, Rozovskaia Tanya, Wassell Richard, Dubois Garrett, Mazo Alexander, Croce Carlo M, Canaani Eli, ALL-1 Is a Histone Methyltransferase that Assembles a Supercomplex of Proteins Involved in Transcriptional Regulation, 10.1016/s1097-2765(02)00740-2
  13. Santos-Rosa Helena, Schneider Robert, Bernstein Bradley E., Karabetsou Nickoletta, Morillon Antonin, Weise Christoph, Schreiber Stuart L., Mellor Jane, Kouzarides Tony, Methylation of Histone H3 K4 Mediates Association of the Isw1p ATPase with Chromatin, 10.1016/s1097-2765(03)00438-6
  14. Bernstein J. A., Khodursky A. B., Lin P.-H., Lin-Chao S., Cohen S. N., Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays, 10.1073/pnas.112318199
  15. Bennett JM, Br J Haematol, 33, 451 (1976)
  16. Bene MC, Leukemia, 9, 1783 (1995)
  17. Van Limbergen Heidi, Poppe Bruce, Michaux Lucienne, Herens Christian, Brown Jill, Noens Luc, Berneman Zwi, De Bock Robrecht, De Paepe Anne, Speleman Frank, Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using m-FISH, 10.1002/gcc.1212
  18. Gabert J, Beillard E, van der Velden V H J, Bi W, Grimwade D, Pallisgaard N, Barbany G, Cazzaniga G, Cayuela J M, Cavé H, Pane F, Aerts J L E, De Micheli D, Thirion X, Pradel V, González M, Viehmann S, Malec M, Saglio G, van Dongen J J M, Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program, 10.1038/sj.leu.2403135
  19. Graux C., Cools J., Melotte C., Quentmeier H., Ferrando A., Levine R., Vermeesch J.R., Stul M., Dutta B., Boeckx N., Bosly A., Heimann P., Uyttebroeck A., Mentens N., Somers R., MacLeod R.A.F., Drexler H.G., Look A.T., Gilliland D.G., Michaux L., Vandenberghe P., Wlodarska I., Marynen Peter, Hagemeijer Anne, Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia, 10.1038/ng1425
  20. Ferrando Adolfo A., Neuberg Donna S., Staunton Jane, Loh Mignon L., Huard Christine, Raimondi Susana C., Behm Fred G., Pui Ching-Hon, Downing James R., Gilliland D.Gary, Lander Eric S., Golub Todd R., Look A.Thomas, Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia, 10.1016/s1535-6108(02)00018-1
  21. Vandesompele Jo, De Preter Katleen, Pattyn Filip, Poppe Bruce, Van Roy Nadine, De Paepe Anne, Speleman Frank, 10.1186/gb-2002-3-7-research0034
  22. Bernard O A, Busson-LeConiat M, Ballerini P, Mauchauffé M, Della Valle V, Monni R, Khac F Nguyen, Mercher T, Penard-Lacronique V, Pasturaud P, Gressin L, Heilig R, Daniel M-T, Lessard M, Berger R, A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia, 10.1038/sj.leu.2402249
  23. Pallisgaard N, Blood, 92, 574 (1998)
  24. Pui CH, Blood, 75, 174 (1990)
  25. Asnafi V., Analysis of TCR, pTalpha , and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment, 10.1182/blood-2002-08-2438
  26. Bergeron J, Clappier E, Cauwelier B, Dastugue N, Millien C, Delabesse E, Beldjord K, Speleman F, Soulier J, Macintyre E, Asnafi V, HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation, 10.1038/sj.leu.2404187
  27. Weng A. P., Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia, 10.1126/science.1102160
  28. Shen WF, Nucleic Acids Res, 19, 539 (1991)
  29. Lowney P, Nucleic Acids Res, 19, 3443 (1991)
  30. Lawrence HJ, Exp Hematol, 23, 1160 (1995)
  31. Zappavigna V, Genes Dev, 8, 732 (1994)
  32. Gisselsson D., Höglund Mattias, Mertens Fredrik, Johansson Bertil, Dal Cin Paola, Van den Berghe Herman, Earnshaw William C., Mitelman Felix, Mandahl Nils, The structure and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells, 10.1007/s004390050960
  33. Gisselsson D., Pettersson L., Hoglund M., Heidenblad M., Gorunova L., Wiegant J., Mertens F., Dal Cin P., Mitelman F., Mandahl N., Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity, 10.1073/pnas.090013497
  34. Nishio Jun, Iwasaki Hiroshi, Ohjimi Yuko, Ishiguro Masako, Isayama Teruto, Naito Masatoshi, Kaneko Yasuhiko, Kikuchi Masahiro, Supernumerary ring chromosomes in dermatofibrosarcoma protuberans may contain sequences from 8q11.2∼qter and 17q21∼qter, 10.1016/s0165-4608(01)00447-2
  35. Nishio Jun, Iwasaki Hiroshi, Ishiguro Masako, Ohjimi Yuko, Yo Sansen, Isayama Teruto, Naito Masatoshi, Kikuchi Masahiro, Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: A fluorescence in situ hybridization and comparative genomic hybridization analysis, 10.1002/1098-2264(2000)9999:9999<::aid-gcc1091>3.3.co;2-i
  36. Streubel Berthold, Valent Peter, Jäger Ulrich, Edelhäuser Martin, Wandt Hannes, Wagner Thomas, Büchner Thomas, Lechner Klaus, Fonatsch Christa, Amplification of the MLL gene on double minutes, a homogeneously staining region, and ring chromosomes in five patients with acute myeloid leukemia or myelodysplastic syndrome, 10.1002/(sici)1098-2264(200004)27:4<380::aid-gcc7>3.3.co;2-r
  37. Andreasson P, Johansson B, Billström R, Garwicz S, Mitelman F, Höglund M, Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements, 10.1038/sj.leu.2400929
  38. Streubel Berthold, Valent Peter, Lechner Klaus, Fonatsch Christa, Amplification of the AML1(CBFA2) gene on ring chromosomes in a patient with acute myeloid leukemia and a constitutional ring chromosome 21, 10.1016/s0165-4608(00)00318-6
  39. Ruiz J C, Choi K H, von Hoff D D, Roninson I B, Wahl G M, Autonomously replicating episomes contain mdr1 genes in a multidrug-resistant human cell line., 10.1128/mcb.9.1.109
  40. Ciullo M., Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I, 10.1093/hmg/11.23.2887
  41. Barr F. G., Nauta L. E., Davis R. J., Schafer B. W., Nycum L. M., Biegel J. A., In Vivo Amplification of the PAX3-FKHR and PAX7-FKHR Fusion Genes in Alveolar Rhabdomyosarcoma, 10.1093/hmg/5.1.15
  42. Rodley Philip, McDonald Margaret, Price Brent, Fright Richard, Morris Christine, Comparative genomic hybridization reveals previously undescribed amplifications and deletions in the chronic myeloid leukemia-derived K-562 cell line, 10.1002/(sici)1098-2264(199705)19:1<36::aid-gcc6>3.0.co;2-1
  43. Marculescu Rodrig, Le Trang, Simon Paul, Jaeger Ulrich, Nadel Bertrand, V(D)J-mediated Translocations in Lymphoid Neoplasms: A Functional Assessment of Genomic Instability by Cryptic Sites, 10.1084/jem.20011578
  44. Raghavan Sathees C., Kirsch Ilan R., Lieber Michael R., Analysis of the V(D)J Recombination Efficiency at Lymphoid Chromosomal Translocation Breakpoints, 10.1074/jbc.m103797200
Bibliographic reference Cauwelier, B. ; Lefebvre, Christine ; Leroux, Dominique ; Poirel, Héléne ; Graux, Carlos ; et. al. Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCR beta-HOXA rearrangement: a study of the Groupe Francophone de Cytogenetique Hematologique. In: Leukemia, Vol. 21, no. 1, p. 121-8 (2007)
Permanent URL http://hdl.handle.net/2078.1/37874