Abstract
Objectives: This study aimed to identify unknown mixed lineage leukemia (MLL) translocation partner genes in a de novo patient with myelodysplastic syndrome (MDS) with t(11;22)(q23;q11) and investigate the clinical and molecular features of this patient.Methods: Bone marrow cells were assessed by karyotype analysis to reveal chromosomal abnormalities. Fluorescence in situ 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.Results: 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.Conclusion: 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.
Highlights
Myelodysplastic syndromes (MDS) are clonal myeloid malignancies characterized by ineffective hematopoiesis, refractory cytopenia, and an increased risk of progression to acute leukemia [1]
Multiple studies have demonstrated that most patients with acute leukemia with mixed lineage leukemia (MLL) rearrangements are characterized by a high degree of MLL-SEPT5 Fusion Transcript in MDS
MLL fusion partner genes are divided into 4 classes: nuclear proteins, cytoplasmic proteins, histone acetyltransferases, and septin gene family members
Summary
Myelodysplastic syndromes (MDS) are clonal myeloid malignancies characterized by ineffective hematopoiesis, refractory cytopenia, and an increased risk of progression to acute leukemia [1]. In contrast to acute leukemia, MLL rearrangement occurs rarely in patients with MDS. Multiple studies have demonstrated that most patients with acute leukemia with MLL rearrangements are characterized by a high degree of MLL-SEPT5 Fusion Transcript in MDS malignancy, low rates of remission, insensitive to chemotherapy, and poor prognosis. Existing literature has found that SEPT5 or EP300 is located at 22q11-22q13 and acts as the translocation partner of MLL [5, 6]. SEPT5 has been precisely identified as a partner of the MLL gene in our patient using LDI-PCR. Patients with MLL gene rearrangement are classified as a distinct subcategory in acute leukemia according to the classification of 2008 WHO [7]. Patients with MDS with MLL gene rearrangement, especially MLL-SEPT fusion, have not been well defined
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