Document Type : Systematic Review and Meta-analysis
Authors
1
Division of Hematology and Medical Oncology, Department of Internal Medicine, Dharmais National Cancer Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
2
Department of Clinical Pathology, Dharmais National Cancer Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
3
Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
4
Department of Pharmacology and Therapeutics, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
5
Department of Internal Medicine, Dharmais National Cancer Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
6
Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Abstract
Objectives: we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk. Materials and Methods: The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) with ID number of CRD42020218581. Systematic literature search was conducted by all authors up to October 2021 on: (1) PubMed, (2) EBSCOhost, (3) Scopus, (4) JSTOR, and (5) grey literatures. Hand-searching for relevant articles was also conducted. The following keywords with their synonyms and combinations using Boolean operators were applied to all database: “myelodysplastic syndrome”, SRSF2”, “SF3B1”, “U2AF1”, “ASXL1”, “DNMT3A”, “TET2”, “IDH1”, “IDH2”, “RUNX1”, “acute myeloid leukemia progression”, and “leukemia free survival”. Outcome was measured using hazard ratio (HR). Results: We identified 14 articles to be used for this systematic review and meta-analysis. There was no statistically significant difference in AML transformation risk between U2AF1 mutant and U2AF1 wildtype MDS patients (HR: 1.41; 95% CI: 0.95–2.07, p=0.08, I2=0%). Pooled HR showed that patients with SRSF2 mutation had higher risk of AML transformation (HR 2.62; 95% CI: 1.54-4.45; p= .0004; I2= 55%). The pooled HR for SF3B1 was 0.48 (95% CI: 0.22–1.06, p=0.07, I2=55%). Mutations of TET2, ASXL1, and EZH2 were not associated with AML transformation. Meanwhile, DNMT3A mutations were associated with AML transformation with pooled HR of 2.73 (95% CI: 1.43-5.21; p= 0.08; I2: 67%). The pooled HR for IDH genes was smaller (HR: 2.92; 95%CI: 1.21-7.06; p=0.02; I2:65%). Patients with RUNX1 mutation were associated with AML transformation (HR: 1.85; 95%CI: 1.11-3.09; p=0.02; I2:38%). Conclusion: Based from our analyses, MDS patients with mutations of SRSF2, DNMT3A, IDH, and RUNX1 have higher hazard ratio for AML transformation.
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