Clinical and molecular characteristics of GATA2 related pediatric primary myelodysplastic syndrome.
10.3760/cma.j.issn.0253-2727.2019.06.006
- VernacularTitle:GATA2突变相关儿童原发性骨髓增生异常综合征临床及分子生物学特征
- Author:
Wen Bin AN
1
,
2
;
Chao LIU
1
,
2
;
Yang WAN
1
,
2
;
Xiao Yan CHEN
1
,
2
;
Ye GUO
3
;
Xiao Juan CHEN
3
;
Wen Yu YANG
3
;
Yu Mei CHEN
3
;
Ying Chi ZHANG
4
;
Xiao Fan ZHU
1
,
2
Author Information
1. Pediatric Blood Diseases Centre, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China
2. State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
3. Pediatric Blood Diseases Centre, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
4. State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
- Publication Type:Journal Article
- Keywords:
GATA2 mutation;
Germline;
Myelodysplastic syndrome;
Pediatric
- MeSH:
Adolescent;
Child;
Child, Preschool;
GATA2 Transcription Factor/genetics*;
Germ-Line Mutation;
Hematopoietic Stem Cell Transplantation;
Humans;
Infant;
Leukemia, Myeloid, Acute;
Myelodysplastic Syndromes/genetics*
- From:
Chinese Journal of Hematology
2019;40(6):477-483
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To clarify the prevalence, clinical features and molecular characteristics of germline GATA2 mutations in pediatric primary myelodysplastic syndromes (MDS) . Methods: Next-generation sequencing technology was used to detect mutations in GATA2 and other myeloid malignancy genes in 129 children with primary MDS from Jan. 2007 to Jan. 2018. The relationship between genotypes and phenotypes was analyzed. Results: Germline GATA2 mutations accounted for 8.5% (11/129) of all primary MDS cases, and 14.0% (11/50) of MDS with excess blasts (MDS-EB) and acute myeloid leukaemia with myelodysplasia-related changes (AML-MRC) . Compared with GATA2 wild-type patients, GATA2 mutated patients were older at diagnosis[8 (1-16) years old vs 6 years old (range: 1 month old-18 years old) , P=0.035]and higher risk of monosomy 7 (72.7%vs 5.2%, P<0.001) and classified into MDS-EB and AML-MRC compared with refractory cytopenia of childhood (RCC) (63.6%vs 36.4%, P=0.111) . The multivariate analysis showed SETBP1 mutation (P=0.041, OR=9.003, 95%CI 1.098-73.787) and isolated monosomy 7 (P=0.002, OR=24.835, 95%CI 3.305-186.620) were significantly associated with germline mutated GATA2. Overall survival (OS) and outcomes of hematopoietic stem cell transplantation (HSCT) were not influenced by GATA2 mutational status. Conclusions: Our data identify germline GATA2 mutations have a high prevalence in older pediatric patients with monosomy 7, and high risk of progression into advanced MDS subtypes. GATA2 mutation status does not affect OS in pediatric primary MDS.
