Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

Wang, L.; Du, Fang; Zhang, H.-M.; Wang, H.-X.

doi:10.1590/1414-431x20154557

Cited by 3 publications

(2 citation statements)

References 15 publications

(17 reference statements)

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“…Other strongly linked hematological malignancies, such as chronic neutrophilic leukemia (CNL), CMML, unclassified MDS, myeloproliferative neoplasms (MPNs), and secondary acute myelocytic leukemia (AML) evolving from MDS [ 25 – 29 ], are also related to SETBP1 . Despite the fact that mutations in both ASXL1 and SETBP1 are generally associated with an adverse prognosis [ 20 , 21 , 26 , 30 ], our patient’s symptoms seemed not to be related to his mutations in these genes. CCAAT enhancer binding protein α (C/EBPα), a general inhibitor of cell proliferation and a tumor suppressor [ 31 ] plays a pivotal role in early granulocyte development.…”

Section: Discussionmentioning

confidence: 60%

A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case

Zhou

Jin

et al. 2017

Mol Cytogenet

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BackgroundChronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones. The oncoprotein tyrosine kinase BCR-ABL1 is a constitutively active kinase involved in the activation of a number of signaling pathways, and it has been the therapeutic target for tyrosine kinase inhibitors (TKIs) such as imatinib. Reports have presented opposing viewpoints about the effect of the disrupted Src homology 3 (SH3) domain on TKI efficacy.FindingsWe here report that using NGS we identified a novel BCR-ABL1 fusion gene with breakpoints in the BCR intron 14 and the ABL1 intron 2, leading to partial deletion of its SH3 domain. In the present case, the patient received targeted therapy with the TKI imatinib at 400 mg/day and no adverse reaction was reported. The patient eventually entered remission with decreased proliferation of karyocytes and granulocytes. We also identified mutations in genes, including TP53, FLT3, ASXL1, SETBP1, CEBPA and CBL, that seemed to have an influence on the outcome of TKI therapy targeting the BCR-ABL1 protein.ConclusionsTogether with previously reported results, it is clear that the genetic heterogeneity of CML patients significantly affects the presentation of the disease and its progression and therefore should inform the design of the therapeutic strategy.

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Section: Discussionmentioning

confidence: 60%

A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case

Zhou

Jin

et al. 2017

Mol Cytogenet

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“…In addition, SETBP1 mutations have been reported to drive leukemic transformation in ASXL transcriptional regulator 1 (ASXL1)-mutated myelodysplastic syndrome (MDS) ( 20 ). Moreover, a father and son diagnosed with atypical chronic myeloid leukemia (aCML) were both found to carry SETBP1 mutations, which are present in 24.3% of aCML patients ( 21 ). Therefore, SETBP1 mutations are believed to be a biomarker in disease diagnosis ( 22 , 23 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of SETBP1 in Gastric Cancer: Friend or Foe

Fang

Liu

et al. 2022

Front. Oncol.

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BackgroundGastric cancer (GC) remains a common disease with a poor prognosis worldwide. The SET binding protein 1 (SETBP1) has been implicated in the pathogenesis of several cancers and plays a dual role as an oncogene and a tumor suppressor gene. However, the role and underlying mechanism of SETBP1 in GC remain unclear.Materials and MethodsWe used next-generation RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) to explore the correlation between SETBP1 expression and tumor progression. We then quantified SETBP1 expression in GC cells with real-time quantitative polymerase chain reactions (RT-qPCR). The chi-square test and logistic regression were used to assess the correlation between SETBP1 expression and clinicopathological features. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the relationship between SETBP1 expression and survival. Finally, gene set enrichment analyses (GSEA) were used to examine GC-related signaling pathways in low and high SETBP1 expressing samples.ResultsWe found SETBP1 expression levels in GC tissues to be significantly lower than in adjacent non-tumor tissues in the TCGA database. In addition, SETBP1 expression differed significantly between groups classified by tumor differentiation. Furthermore, SETBP1 expression in diffuse-type GC was significantly higher than in intestinal-type GC. However, it did not differ significantly across pathological- or T-stage groups. RT-qPCR and comprehensive meta-analysis showed that SETBP1 expression is downregulated in GC cells and tissues. Interestingly, SETBP1 expression in poorly- or un-differentiated GC cells was higher than in well-differentiated GC cells. Moreover, the chi-square test and logistic regression analyses showed that SETBP1 expression correlates significantly with tumor differentiation. Kaplan–Meier curves indicated that patients with relatively high SETBP1 expression had a poor prognosis. Multivariate analyses indicated that SETBP1 expression might be an important predictor of poor overall survival in GC patients. GSEA indicated that 20 signaling pathways were significantly enriched in samples with high and low SETBP1 expression.ConclusionSETBP1 may play a dual role in GC progression.

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Cyclophosphamide/hydroxycarbamide/imatinib

2022

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Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

Cited by 3 publications

References 15 publications

A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case

A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case

The Role of SETBP1 in Gastric Cancer: Friend or Foe

Cyclophosphamide/hydroxycarbamide/imatinib

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