Duployez Nicolas, Boudry-Labis Elise, Roumier Christophe, Boissel Nicolas, Petit Arnaud, Geffroy Sandrine, Helevaut Nathalie, Celli-Lebras Karine, Terré Christine, Fenneteau Odile, Cuccuini Wendy, Luquet Isabelle, Lapillonne Hélène, Lacombe Catherine, Cornillet Pascale, Ifrah Norbert, Dombret Hervé, Leverger Guy, Jourdan Eric, Preudhomme Claude
CHU Lille, Laboratory of Hematology, Biology and Pathology Center, Lille, France.
Univ. Lille, INSERM, UMR-S 1172, JPARC, Lille, France.
Oncotarget. 2018 Jan 8;9(5):6478-6489. doi: 10.18632/oncotarget.24031. eCollection 2018 Jan 19.
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. mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried truncating mutations. Finally, 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.
伴有t(8;21)和inv(16)的急性髓系白血病（AML），统称为核心结合因子（CBF）-AML，被认为是独特的实体。这两种重排具有共同的病理生理学特征，即CBF的破坏，且预后相对较好。实验表明，CBF重排不足以诱发白血病，这意味着存在协同事件。为了探究这些异常，我们在一个有详细注释的包含198例CBF-AML患者的队列中进行了单核苷酸多态性（SNP）阵列分析。排除与断点相关的病变，最常见的事件包括t(8;21)患者中一条性染色体丢失（53%）、9q21缺失（12%）和7q36缺失（9%），而inv(16)患者中22号染色体三体（13%）、8号染色体三体（10%）和7q36缺失（12%）。SNP阵列揭示了可能参与CBF-AML白血病发生的新的复发性基因改变。19p染色体杂合性拷贝中性缺失（CN-LOH）的靶点显示为突变（占t(8;21)-AML的20%）。在5%的inv(16)-AML中发现了局灶性缺失，而序列分析显示2%携带截短突变。最后，在两种亚型中均发现了[此处原文似乎缺失部分内容]破坏（占整个队列的4.5%），这可能突出了与这种特殊亚型白血病中异常酪氨酸激酶信号传导相关的一种新病变。
