Department of Haematology, Christian Medical College, Vellore, India.
Int J Lab Hematol. 2021 Aug;43(4):658-663. doi: 10.1111/ijlh.13580. Epub 2021 May 14.
ZNF384 gene fusions resulting from translocations with several partner genes have been described in B cell acute lymphoblastic leukemia (B-ALL) with a characteristic immunophenotype (aberrant CD13 and or CD33 with dim CD10). The prognosis of patients with this rearrangement appears to depend on the fusion partner. ZNF384 rearrangements have been identified by high through put technologies such as RNA sequencing in most of the studies published. We tested the feasibility of using the characteristic immunophenotype as a tool to screen for patients with ZNF384 translocations which can be subsequently confirmed by cytogenetic / molecular methodologies.
ZNF384 rearrangements in B-ALL patients at diagnosis with CD10 <80% and were negative for the BCR-ABL1 fusion (n = 109) were identified by fluorescence in situ hybridization followed by confirmation by reverse transcriptase-polymerase chain reaction and Sanger sequencing. The end of induction measurable residual disease evaluated by flow cytometry for these patients was obtained from patient records.
ZNF384 translocations were identified in 14 patients and were cytogenetically cryptic in 13. EP300-ZNF384 was the most common fusion partner (n = 12), while TAF15-ZNF384 and TCF3-ZNF384 were identified in 1 patient each. End of induction MRD by flow cytometry was positive in 5 of 8 patients with the EP300-ZNF384 fusion treated at our center.
Our findings show a practical approach for the identification of ZNF384 gene rearrangements by widely available technologies and indicate that the response to therapy may be heterogeneous even in this subset, which has been reported as having a favorable prognosis.
已经描述了与几个伙伴基因易位导致的 ZNF384 基因融合在具有特征性免疫表型（异常 CD13 和/或 CD33 伴 CD10 减弱）的 B 细胞急性淋巴细胞白血病（B-ALL）中。这种重排的患者预后似乎取决于融合伙伴。在大多数已发表的研究中，通过高通量技术（如 RNA 测序）已鉴定出 ZNF384 重排。我们测试了使用特征性免疫表型作为工具来筛选 ZNF384 易位患者的可行性，这些患者可以通过细胞遗传学/分子方法学随后确认。
通过荧光原位杂交鉴定诊断时 CD10 <80%且无 BCR-ABL1 融合的 B-ALL 患者中 ZNF384 重排（n = 109），随后通过逆转录-聚合酶链反应和 Sanger 测序确认。这些患者的诱导结束时可测量的残留疾病通过流式细胞术从患者记录中获得。
在 14 名患者中鉴定出 ZNF384 易位，其中 13 例为细胞遗传学隐匿性。EP300-ZNF384 是最常见的融合伙伴（n = 12），而 TAF15-ZNF384 和 TCF3-ZNF384 分别在 1 名患者中发现。在我们中心治疗的 8 名 EP300-ZNF384 融合患者中，有 5 名患者在诱导结束时流式细胞术的 MRD 为阳性。
我们的发现表明了一种通过广泛可用的技术识别 ZNF384 基因重排的实用方法，并表明即使在这种被报道预后良好的亚组中，治疗反应也可能存在异质性。
