Fournier Benjamin, Balducci Estelle, Duployez Nicolas, Clappier Emmanuelle, Cuccuini Wendy, Arfeuille Chloé, Caye-Eude Aurélie, Delabesse Eric, Bottollier-Lemallaz Colomb Elodie, Nebral Karin, Chrétien Marie-Lorraine, Derrieux Coralie, Cabannes-Hamy Aurélie, Dumezy Florent, Etancelin Pascaline, Fenneteau Odile, Frayfer Jamile, Gourmel Antoine, Loosveld Marie, Michel Gérard, Nadal Nathalie, Penther Dominique, Tigaud Isabelle, Fournier Elise, Reismüller Bettina, Attarbaschi Andishe, Lafage-Pochitaloff Marina, Baruchel André
Department of Pediatric Hematology and Immunology, University Hospital Robert Debré, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
Hematology Laboratory, University Hospital Paul-Brousse, Assistance Publique des Hôpitaux de Paris (APHP), Villejuif, France.
Front Oncol. 2019 Dec 10;9:1374. doi: 10.3389/fonc.2019.01374. eCollection 2019.
B-cell acute lymphoblastic leukemia associated with t(5;14)(q31;q32); is an exceptional cause of eosinophilia. The enhancer on 14q32 is juxtaposed to the gene on 5q31, leading to interleukin-3 overproduction and release of mature eosinophils in the blood. Clinical, biological and outcome data are extremely scarce in the literature. Except for eosinophilia, no relevant common feature has been highlighted in these patients. However, it has been classified as a distinct entity in the World Health Organization classification. Eight patients with t(5;14)(q31;q32) treated by French or Austrian protocols were retrospectively enrolled. Array comparative genomic hybridization, multiplex ligation-dependent probe amplification or genomic PCR search for deletion were performed in 7. Sixteen patients found through an exhaustive search in the literature were also analyzed. For those 24 patients, median age at diagnosis is 14.3 years with a male predominance (male to female ratio = 5). Eosinophilia-related symptoms are common (neurologic in 26%, thromboembolic in 26% or pulmonary in 50%). Median white blood cells count is high (72 × 10/L) and linked to eosinophilia (median: 32 × 10/L). Peripheral blasts are present at a low level or absent (median: 0 × 10/L; range: 0-37 × 10/L). Bone marrow morphology is marked by a low blast infiltration (median: 42%). We found an deletion in 5 out of 7 analyzable patients Outcome data are available for 14 patients (median follow-up: 28 months): 8 died and 6 are alive in complete remission. Some of these features are concordant with those seen in patients with other -rearranged B-cell acute lymphoblastic leukemias: young age at onset, male sex, low blast count, high incidence of deletion and intermediate prognosis. Based on shared epidemiological and biological features, B-cell acute lymphoblastic leukemia with t(5;14)(q31;q32) is a peculiar subset of -rearranged B-cell acute lymphoblastic leukemia with an intermediate prognosis and particular clinical features related to eosinophilia.
与t(5;14)(q31;q32)相关的B细胞急性淋巴细胞白血病是嗜酸性粒细胞增多的罕见原因。14号染色体长臂q32上的增强子与5号染色体长臂q31上的基因并列，导致白细胞介素-3过度产生并使成熟嗜酸性粒细胞释放入血。文献中临床、生物学及预后数据极为匮乏。除嗜酸性粒细胞增多外，这些患者未发现相关共同特征。然而，在世界卫生组织分类中它被归为一个独特实体。回顾性纳入了8例按法国或奥地利方案治疗的t(5;14)(q31;q32)患者。对其中7例进行了阵列比较基因组杂交、多重连接依赖探针扩增或基因组PCR检测以寻找ETV6缺失。还对通过文献全面检索找到的16例患者进行了分析。对于这24例患者，诊断时的中位年龄为14.3岁，男性居多（男女性别比 = 5）。与嗜酸性粒细胞增多相关的症状常见（26%有神经系统症状，26%有血栓栓塞症状，50%有肺部症状）。中位白细胞计数较高（72×10⁹/L）且与嗜酸性粒细胞增多相关（中位值：32×10⁹/L）。外周血原始细胞水平低或无（中位值：0×10⁹/L；范围：0 - 37×！0⁹/L）。骨髓形态学特征为原始细胞浸润低（中位值：42%）。7例可分析患者中有5例发现有ETV6缺失。14例患者有预后数据（中位随访时间：28个月）：8例死亡，6例完全缓解存活。其中一些特征与其他ETV6重排的B细胞急性淋巴细胞白血病患者所见特征一致：发病年龄小、男性、原始细胞计数低、ETV6缺失发生率高及预后中等。基于共同的流行病学和生物学特征，伴有t(5;14)(q31;q32)的B细胞急性淋巴细胞白血病是ETV6重排的B细胞急性淋巴细胞白血病的一个特殊亚组，预后中等且有与嗜酸性粒细胞增多相关的特殊临床特征。
