Zou Duobing, Chen Ying, Wu Ningning, Zhang Yi, Ouyang Guifang, Mu Qitian
Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Ningbo, China.
Department of Hematology, Ningbo First Hospital, Ningbo, China.
Front Med (Lausanne). 2021 Dec 22;8:783229. doi: 10.3389/fmed.2021.783229. eCollection 2021.
This study aimed to identify unknown mixed lineage leukemia (MLL) translocation partner genes in a patient with myelodysplastic syndrome (MDS) with t(11;22)(q23;q11) and investigate the clinical and molecular features of this patient. Bone marrow cells were assessed by karyotype analysis to reveal chromosomal abnormalities. Fluorescence hybridization (FISH) was performed to detect MLL gene rearrangement using an MLL-specific break-apart probe. LDI-PCR and RT-PCR were performed, and the PCR products were sequenced using an Illumina MiSeq sequencer (Illumina, San Diego, CA, USA). The sequence data of the PCR products were analyzed using bioinformatics tools. Meanwhile, clinical data were collected to evaluate the prognosis of the patient. Chromosomal karyotype analysis showed that the karyotype of the patient was 46, XX, t(11;22)(q23;q11)[10]/46, XX[1]. Subsequently, FISH data confirmed MLL gene rearrangement in the patient. LDI-PCR precisely showed that SEPT5 was the MLL translocation partner gene. RT-PCR and sequencing analysis disclosed the presence of MLL-SEPT5 fusion transcript and confirmed the fusion between MLL exon 8 and SEPT5 exon 3. Moreover, the patient had a recurrence shortly after allogeneic hematopoietic stem cell transplantation. Although the MLL-SEPT5 fusion transcript was occasionally described in acute myeloid leukemia, it was first identified in MDS. Patients with MLL-SEPT5 fusion gene exhibited a poor prognosis even with an aggressive treatment.
本研究旨在鉴定一名患有伴t(11;22)(q23;q11)的骨髓增生异常综合征（MDS）患者中未知的混合谱系白血病（MLL）易位伙伴基因，并研究该患者的临床和分子特征。通过核型分析评估骨髓细胞以揭示染色体异常。使用MLL特异性断裂分离探针进行荧光杂交（FISH）以检测MLL基因重排。进行长距离PCR（LDI-PCR）和逆转录PCR（RT-PCR），并使用Illumina MiSeq测序仪（美国加利福尼亚州圣地亚哥的Illumina公司）对PCR产物进行测序。使用生物信息学工具分析PCR产物的序列数据。同时，收集临床数据以评估患者的预后。染色体核型分析显示该患者的核型为46,XX,t(11;22)(q23;q11)[10]/46,XX[1]。随后，FISH数据证实该患者存在MLL基因重排。LDI-PCR精确显示SEPT5是MLL易位伙伴基因。RT-PCR和测序分析揭示了MLL-SEPT5融合转录本的存在，并证实了MLL外显子8与SEPT5外显子3之间的融合。此外，该患者在异基因造血干细胞移植后不久复发。尽管MLL-SEPT5融合转录本在急性髓系白血病中偶尔有描述，但它首次在MDS中被鉴定出来。具有MLL-SEPT5融合基因的患者即使接受积极治疗，预后也较差。
