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Database-guided Flow-cytometry for Evaluation of Bone Marrow Myeloid Cell Maturation
Published on: November 3, 2018
Reduced expression of FLIP SHORT in bone marrow of low risk myelodysplastic syndrome
Paula de Melo Campos1, Fabíola Traina, Adriana da Silva Santos Duarte
1Haematology and Hemotherapy Centre, Department of Internal Medicine, State University of Campinas, SP, Brazil.
Abstract:
Apoptosis is dysregulated in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukaemia (AML). FLIP (FLICE (FAS-associated death-domain-like IL-1 beta-converting enzyme)-inhibitory protein) has been described as an anti-apoptotic protein. Here, we characterize the expression level of FLIP(LONG) and FLIP(SHORT) mRNA in bone marrow aspirates from 61 patients diagnosed with MDS or AML. FLIP(SHORT) mRNA expression was significantly lower in low risk MDS, compared to high risk MDS, according to FAB classification (RA/RARS versus RAEB/RAEBt, P=0.0127) and IPSS (low risk/intermediate-1 versus intermediate-2/high risk, P=0.0345). Furthermore, FLIP(SHORT) mRNA expression was significantly lower in low risk MDS, compared to MDS-AML/AML de novo (P=0.0006), according to FAB classification. FLIP(LONG) expression did not differ between these groups. Increased levels of FLIP(SHORT) in RAEB and AML may be related to apoptosis resistance in these diseases and to MDS progression.
Insights
FLIP(SHORT) mRNA levels are significantly lower in low-risk myelodysplastic syndromes (MDS) compared to high-risk MDS and acute myelogenous leukemia (AML). This finding suggests FLIP(SHORT) may play a role in disease progression and apoptosis resistance.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Apoptosis dysregulation is a hallmark of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).
- FLIP (FLICE-inhibitory protein) is an anti-apoptotic protein implicated in cancer cell survival.
Purpose of the Study:
- To investigate the expression levels of FLIP(LONG) and FLIP(SHORT) mRNA in patients with MDS and AML.
- To correlate FLIP mRNA expression with disease risk and classification.
Main Methods:
- Bone marrow aspirates from 61 patients with MDS or AML were analyzed.
- Quantitative analysis of FLIP(LONG) and FLIP(SHORT) mRNA expression levels was performed.
Main Results:
- FLIP(SHORT) mRNA expression was significantly lower in low-risk MDS compared to high-risk MDS (FAB and IPSS classifications).
- FLIP(SHORT) mRNA expression was significantly lower in low-risk MDS compared to MDS-AML/AML de novo (FAB classification).
- No significant difference in FLIP(LONG) expression was observed between the groups.
Conclusions:
- Reduced FLIP(SHORT) mRNA expression is associated with lower-risk MDS.
- Elevated FLIP(SHORT) in higher-risk MDS and AML may contribute to apoptosis resistance and disease progression.
