Research Papers:

SNP-array lesions in core binding factor acute myeloid leukemia

Nicolas Duployez, Elise Boudry-Labis, Christophe Roumier, Nicolas Boissel, Arnaud Petit, Sandrine Geffroy, Nathalie Helevaut, Karine Celli-Lebras, Christine Terre, Odile Fenneteau, Wendy Cuccuini, Isabelle Luquet, Helene Lapillonne, Catherine Lacombe, Pascale Cornillet, Norbert Ifrah, Herve Dombret, Guy Leverger, Eric Jourdan and Claude Preudhomme _

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Oncotarget. 2018; 9:6478-6489. https://doi.org/10.18632/oncotarget.24031

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Nicolas Duployez1,2, Elise Boudry-Labis2,3, Christophe Roumier1,2, Nicolas Boissel4, Arnaud Petit5,6, Sandrine Geffroy1,2, Nathalie Helevaut1,2, Karine Celli-Lebras4, Christine Terré7, Odile Fenneteau8, Wendy Cuccuini9, Isabelle Luquet10, Hélène Lapillonne6,11, Catherine Lacombe12, Pascale Cornillet13, Norbert Ifrah14, Hervé Dombret4, Guy Leverger5,6, Eric Jourdan15 and Claude Preudhomme1,2

1CHU Lille, Laboratory of Hematology, Biology and Pathology Center, Lille, France

2Univ. Lille, INSERM, UMR-S 1172, JPARC, Lille, France

3CHU Lille, Institute of Medical Genetics, Jeanne de Flandre Hospital, Lille, France

4APHP, Department of Hematology, Saint Louis Hospital, Paris, France

5APHP, Department of Pediatric Hematology and Oncology, GH HUEP, Trousseau Hospital, Paris, France

6Sorbonne Universites, UPMC Univ Paris 06, UMR-S 938, CDR Saint-Antoine, GRC n°07, GRC MyPAC, Paris, France

7CH Versailles, Department of Genetics, Le Chesnay, France

8APHP, Laboratory of Hematology, Robert Debré University Hospital, Paris, France

9APHP, Department of Cytogenetics, Saint Louis Hospital, Paris, France

10CHU Toulouse, Laboratory of Hematology, Toulouse, France

11APHP, Laboratory of Hematology, GH HUEP, Trousseau Hospital, Paris, France

12APHP, Goelamsthèque, Cochin Hospital, Paris, France

13CHU Reims, Laboratory of Hematology, Reims, France

14CHU Angers, INSERM CRCINA, Department of Hematology, Angers, France

15CHU Nîmes, Department of Hematology, Nîmes, France

Correspondence to:

Claude Preudhomme, email: [email protected]

Nicolas Duployez, email: [email protected]

Keywords: acute myeloid leukemia; core binding factor; SNP-array; sequencing

Received: November 21, 2017     Accepted: January 03, 2018     Published: January 08, 2018


Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia.

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