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Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes
Masayuki Shiseki1, Mayuko Ishii1, Mari Miyazaki1
1Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
Abstract:
The PLCG1 gene, which encodes the phospholipase C γ1 isoform, is located within the commonly deleted region of the long arm of chromosome 20 (del(20q)) observed in myelodysplastic syndromes (MDS). Phospholipase C is involved in diverse physiological and pathological cellular processes through inositide signaling. We hypothesized that reduced PLCG1 expression because of haploinsufficiency by del(20q) plays a role in the molecular pathogenesis of MDS. Therefore, we analyzed PLCG1 expression in bone marrow mononuclear cells at diagnosis in 116 MDS patients with or without del(20q) by quantitative RT-PCR to evaluate its clinical significance. The expression level of PLCG1 was significantly lower not only in MDS patients with del(20q) but also in those without del(20q) compared to that of the controls, which suggests that reduced PLCG1 expression is a common molecular event in MDS. Patients in the lowest quartile (Q4) group for PLCG1 expression had lower overall survival (OS) compared to that of other patients (Q1-Q3) (log-rank test, P = .0004) with estimated median OS times of 22 in the Q4 group and 106 months in the Q1-3 group. Univariate and multivariate analysis indicated reduced PLCG1 expression (Q4) was associated with lower OS (hazard ratio 2.58, 95% CI 1.35-4.84, P = .0049), which suggests that reduced PLCG1 expression is an independent prognostic factor for OS. In addition, patients were well-stratified for OS by combining PLCG1 expression level (Q4 vs Q1-3) and bone marrow blast percentage (5% or more vs less than 5%). Thus, the level of PLCG1 expression at time of diagnosis is a prognostic biomarker for MDS.
Insights
Reduced phospholipase C gamma 1 (PLCG1) gene expression is common in myelodysplastic syndromes (MDS). Lower PLCG1 levels indicate poorer overall survival and serve as an independent prognostic factor for MDS patients.
Area of Science:
- Genetics and Molecular Biology
- Hematology
- Oncology
Background:
- The PLCG1 gene, encoding phospholipase C gamma 1, is located in the del(20q) region frequently observed in myelodysplastic syndromes (MDS).
- Phospholipase C is crucial for inositide signaling, impacting cellular processes in both health and disease.
Purpose of the Study:
- To investigate the role of reduced PLCG1 expression, potentially due to del(20q) haploinsufficiency, in the molecular pathogenesis of MDS.
- To evaluate the clinical significance of PLCG1 expression levels as a prognostic biomarker in MDS.
Main Methods:
- Quantitative RT-PCR was used to analyze PLCG1 expression in bone marrow mononuclear cells from 116 MDS patients and controls.
- Statistical analyses, including log-rank tests and univariate/multivariate analyses, were performed to assess the association between PLCG1 expression and overall survival (OS).
Main Results:
- Significantly lower PLCG1 expression was observed in MDS patients (with or without del(20q)) compared to controls, suggesting it's a common event in MDS.
- Patients with the lowest PLCG1 expression (Q4) had significantly lower OS (median 22 months) compared to those with higher expression (Q1-3, median 106 months).
- Reduced PLCG1 expression was identified as an independent prognostic factor for OS in MDS (HR 2.58, P=.0049).
Conclusions:
- Reduced PLCG1 expression is a common molecular event in MDS and an independent prognostic biomarker for overall survival.
- Combining PLCG1 expression levels with bone marrow blast percentage can effectively stratify MDS patients for OS.
