Hirabayashi Shinsuke, Wlodarski Marcin W, Kozyra Emilia, Niemeyer Charlotte M
Department of Pediatrics, St. Luke's InternationalHospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, 1048560, Japan.
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Int J Hematol. 2017 Aug;106(2):175-182. doi: 10.1007/s12185-017-2285-2. Epub 2017 Jun 22.
The GATA2 gene codes for a master hematopoietic transcription factor that is essential for the proliferation and maintenance of hematopoietic stem and progenitor cells. Heterozygous germline mutations in GATA2 have been initially associated with several clinical entities that are now collectively defined as GATA2 deficiency. Despite pleiotropic clinical manifestations, the high propensity for the development of myelodysplastic syndromes (MDS) constitutes the most common clinical denominator of this major MDS predisposition syndrome. The immunological phenotypes can be variable and mostly include deficiency of monocytes and/or B cells. Thus far, nearly 380 GATA2-deficient patients had been reported, with a roughly estimated prevalence of myeloid neoplasia of at least 75%. The most common abnormal karyotypes associated with GATA2-related MDS are monosomy 7, der(1;7) and trisomy 8. The overall clinical penetrance seems to be nearly complete for this transcriptopathy disorder. The high-risk MDS subtypes and karyotypes, and the underlying immunodeficiency guide decision-making toward timely stem cell transplantation.
GATA2基因编码一种主要的造血转录因子，该因子对于造血干细胞和祖细胞的增殖及维持至关重要。GATA2基因的杂合种系突变最初与多种临床病症相关，这些病症现在统称为GATA2缺陷。尽管有多种临床表现，但骨髓增生异常综合征（MDS）的高发倾向构成了这种主要的MDS易感综合征最常见的临床特征。免疫表型可能各异，主要包括单核细胞和/或B细胞缺乏。迄今为止，已报告了近380例GATA2缺陷患者，据粗略估计，髓系肿瘤的患病率至少为75%。与GATA2相关的MDS相关的最常见异常核型是7号染色体单体、der(1;7)和8号染色体三体。这种转录病的总体临床外显率似乎几乎是完全的。高危MDS亚型和核型以及潜在的免疫缺陷指导着及时进行干细胞移植的决策。
