Nada Assaf1, Raphael Liévin2,3, Fatiha Merabet2,3, Victoria Raggueneau4, Jenifer Osman4, Rathana Kim5,6, Francine Garnache7, Mariella D'Angiò8, Patrizia Larghero9, Claus Meyer9, Rolf Marschalek9, Philippe Rousselot2,3, Christine Terré10. 1. Department of Laboratory Medicine, Hemato-Oncologic Cytogenetics, Centre Hospitalier de Versailles, 2, rue JL Forain, 78150, Le Chesnay, France. assaf.nada@outlook.com. 2. Department of Hematology, Centre Hospitalier de Versailles, Le Chesnay, France. 3. University Paris-Saclay, UMR1184, Gif-sur-Yvette, France. 4. Department of Laboratory Medicine, Hematology, Centre Hospitalier de Versailles, Le Chesnay, France. 5. Hematology Laboratory, Hôpital Saint-Louis, APHP, Paris, France. 6. Université de Paris, INSERM U944, CNRS UMR 7212, Paris, France. 7. Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Besançon, France. 8. Department of Pediatrics, Centro Ricerca Tettamanti, San Gerardo Hospital/Fondazione MBBM, University of Milan Bicocca, Monza, Italy. 9. Institute of Pharmaceutical Biology/DCAL, Goethe-University Frankfurt, Frankfurt am Main, Germany. 10. Department of Laboratory Medicine, Hemato-Oncologic Cytogenetics, Centre Hospitalier de Versailles, 2, rue JL Forain, 78150, Le Chesnay, France.
Abstract
BACKGROUND: The detection of KMT2A gene rearrangements have an important impact on the prognosis and management of acute leukemias. These alterations most commonly involve reciprocal translocations at specific breakpoint regions within KMT2A. To date, more than 100 translocation partner genes of KMT2A have been identified, with different effects on risk stratification. METHODS AND RESULTS: We report the case of a mature plasmacytoid dendritic cells proliferation associated with B lymphoblasts harboring a KMT2A-ARHGEF12 fusion. This rare rearrangement, resulting from a cryptic deletion on the long arm of chromosome 11, is located outside the known major and minor breakpoint regions of KMT2A, not reported to date. The review of the few cases of KMT2A-ARHGEF12 reveals the tendency of this deletion to occur in therapy related hematologic neoplasm and confer unfavorable prognosis. CONCLUSION: This review sheds light into the rare KMT2A-ARHGEF12 fusion in leukemia. Reporting rare chimeras is essential to improve knowledge about the biological mechanism and associated clinical consequences.
BACKGROUND: The detection of KMT2A gene rearrangements have an important impact on the prognosis and management of acute leukemias. These alterations most commonly involve reciprocal translocations at specific breakpoint regions within KMT2A. To date, more than 100 translocation partner genes of KMT2A have been identified, with different effects on risk stratification. METHODS AND RESULTS: We report the case of a mature plasmacytoid dendritic cells proliferation associated with B lymphoblasts harboring a KMT2A-ARHGEF12 fusion. This rare rearrangement, resulting from a cryptic deletion on the long arm of chromosome 11, is located outside the known major and minor breakpoint regions of KMT2A, not reported to date. The review of the few cases of KMT2A-ARHGEF12 reveals the tendency of this deletion to occur in therapy related hematologic neoplasm and confer unfavorable prognosis. CONCLUSION: This review sheds light into the rare KMT2A-ARHGEF12 fusion in leukemia. Reporting rare chimeras is essential to improve knowledge about the biological mechanism and associated clinical consequences.
Authors: P J Kourlas; M P Strout; B Becknell; M L Veronese; C M Croce; K S Theil; R Krahe; T Ruutu; S Knuutila; C D Bloomfield; M A Caligiuri Journal: Proc Natl Acad Sci U S A Date: 2000-02-29 Impact factor: 11.205
Authors: T Burmeister; R Marschalek; B Schneider; C Meyer; N Gökbuget; S Schwartz; D Hoelzer; E Thiel Journal: Leukemia Date: 2006-03 Impact factor: 11.528
Authors: V H J Van der Velden; L Corral; M G Valsecchi; M W J C Jansen; P De Lorenzo; G Cazzaniga; E R Panzer-Grümayer; M Schrappe; A Schrauder; C Meyer; R Marschalek; L L Nigro; M Metzler; G Basso; G Mann; M L Den Boer; A Biondi; R Pieters; J J M Van Dongen Journal: Leukemia Date: 2009-02-12 Impact factor: 11.528
Authors: C Meyer; T Burmeister; D Gröger; G Tsaur; L Fechina; A Renneville; R Sutton; N C Venn; M Emerenciano; M S Pombo-de-Oliveira; C Barbieri Blunck; B Almeida Lopes; J Zuna; J Trka; P Ballerini; H Lapillonne; M De Braekeleer; G Cazzaniga; L Corral Abascal; V H J van der Velden; E Delabesse; T S Park; S H Oh; M L M Silva; T Lund-Aho; V Juvonen; A S Moore; O Heidenreich; J Vormoor; E Zerkalenkova; Y Olshanskaya; C Bueno; P Menendez; A Teigler-Schlegel; U Zur Stadt; J Lentes; G Göhring; A Kustanovich; O Aleinikova; B W Schäfer; S Kubetzko; H O Madsen; B Gruhn; X Duarte; P Gameiro; E Lippert; A Bidet; J M Cayuela; E Clappier; C N Alonso; C M Zwaan; M M van den Heuvel-Eibrink; S Izraeli; L Trakhtenbrot; P Archer; J Hancock; A Möricke; J Alten; M Schrappe; M Stanulla; S Strehl; A Attarbaschi; M Dworzak; O A Haas; R Panzer-Grümayer; L Sedék; T Szczepański; A Caye; L Suarez; H Cavé; R Marschalek Journal: Leukemia Date: 2017-07-13 Impact factor: 11.528