PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies
PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies
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DOI：
10.1111/j.1365-2141.2011.08918.x
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发表时间：
2012-01-01
影响因子：
6.5
通讯作者：
Poirel, Helene A.
中科院分区：
文献类型：
--
作者：
Duhoux, Francois P.;Ameye, Genevieve;Poirel, Helene A.
PRDM16 (1p36) 基因在急性髓性白血病 (AML) 和骨髓增生异常综合征 (MDS) 中重排，具有 t(1;3)(p36;q21)，与具有 MECOM (3q26.2) 易位的 AML 和 MDS 具有相同的特征。我们使用荧光原位杂交研究了 39 种涉及 PRDM16 易位的血液恶性肿瘤，以评估 1p36 上的精确断点和伙伴基因座的身份。在选定的病例中进行了逆转录聚合酶链反应（PCR），以确认伴侣基因座。使用 TaqMan 实时定量 PCR 对患者、正常对照和 CD34+ 细胞的骨髓样本进行 PRDM16 表达研究。 PRDM16 在 30 例中与 RPN1 (3q21) 基因座重排，在 9 例中与其他基因座重排。除两例淋巴样增生外，大多数病例诊断为 AML 或 MDS。我们鉴定了 PRDM16 的新易位伙伴，包括转录因子 ETV6 和 IKZF1。无论重排（融合基因或启动子交换）的结果如何，涉及 PRDM16 的易位都会导致其过度表达。生存数据表明，尽管核型简单且中位年龄为 65 岁，但患有 AML/MDS 和 PRDM16 易位的患者预后较差。与迟发性治疗相关的骨髓恶性肿瘤似乎过多。
The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34+ cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.