Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes
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 throu...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2717 |
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| author | Masayuki Shiseki Mayuko Ishii Mari Miyazaki Satoko Osanai Yan‐Hua Wang Kentaro Yoshinaga Naoki Mori Junji Tanaka |
| author_facet | Masayuki Shiseki Mayuko Ishii Mari Miyazaki Satoko Osanai Yan‐Hua Wang Kentaro Yoshinaga Naoki Mori Junji Tanaka |
| author_sort | Masayuki Shiseki |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e7059046425c4fd9a85dbfb08bc2d4d5 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-e7059046425c4fd9a85dbfb08bc2d4d52025-08-25T10:14:04ZengWileyCancer Medicine2045-76342020-01-019246046810.1002/cam4.2717Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromesMasayuki Shiseki0Mayuko Ishii1Mari Miyazaki2Satoko Osanai3Yan‐Hua Wang4Kentaro Yoshinaga5Naoki Mori6Junji Tanaka7Department of Hematology Tokyo Women's Medical University Tokyo JapanDepartment of Hematology Tokyo Women's Medical University Tokyo JapanDepartment of Hematology Tokyo Women's Medical University Tokyo JapanDepartment of Hematology Tokyo Women's Medical University Tokyo JapanDepartment of Hematology Tokyo Women's Medical University Tokyo JapanDepartment of Hematology Tokyo Women's Medical University Tokyo JapanDepartment of Hematology Tokyo Women's Medical University Tokyo JapanDepartment of Hematology Tokyo Women's Medical University Tokyo JapanAbstract 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.https://doi.org/10.1002/cam4.2717common deleted regiondel(20q)haploinsufficiencyMDSPLCG1 |
| spellingShingle | Masayuki Shiseki Mayuko Ishii Mari Miyazaki Satoko Osanai Yan‐Hua Wang Kentaro Yoshinaga Naoki Mori Junji Tanaka Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes Cancer Medicine common deleted region del(20q) haploinsufficiency MDS PLCG1 |
| title | Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes |
| title_full | Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes |
| title_fullStr | Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes |
| title_full_unstemmed | Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes |
| title_short | Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes |
| title_sort | reduced plcg1 expression is associated with inferior survival for myelodysplastic syndromes |
| topic | common deleted region del(20q) haploinsufficiency MDS PLCG1 |
| url | https://doi.org/10.1002/cam4.2717 |
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