Gene expression of hematopoietic transcription factors in pediatric acute megakaryocytic leukemia

小儿急性巨核细胞白血病造血转录因子基因表达

基本信息

批准号：
20591251
负责人：
YAGASAKI Hiroshi
金额：
$ 2.83万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

Acute megakaryoblastic leukemia (AMKL) has a diverse heterogeneity of the disease including morphology and cytogenetic studies. In children, 2 major subgroups have been described : AMKL developing in patients with Down syndrome (DS-AMKL) and AMKL in patients without Down syndrome (non-DS-AMKL). To compare the biological characteristics of blast cells with DS-AMKL and non-DS-AMKL, we compared the expression of hematopoietic transcription factors in blast cells derived from 19 children with AMKL (DS-AMKL : 11, non-DS-AMKL : 9). The morphology of blast cells was categorized into four groups : type 1, completely undifferentiated blasts ; type 2, intermediately differentiated blasts with cytoplasmic blebs ; type 3, blasts with dysmegakaryocytopoiesis ; type 4, blasts with deep blue cytoplasm. To define the differentiation stage by molecular level, we quantified the expression of transcription factors related to megakaryo-erythroid cell lineages ; GATA1, GATA2, FOG-1, NF-E2, SCL, PU.1, C/EBPα, c-mpl, Epo-R, CD41b, βglobin. In conclusion, blasts of DS-AMKL differentiated into not only megakaryocyte but also erythroid lineage because of overexpression of glycophorin A and βglobin under the GATA1 gene mutations. DS-AMKL should be classified into other categories apart from non-DS-AMKL considering the totally different patterns in gene alterations and levels of transcription factors.

急性巨毛细胞白血病（AMKL）具有疾病的不同异质性，包括形态学和细胞遗传学研究。在儿童中，已经描述了2个主要亚组：唐氏综合症患者（DS-AMKL）和无唐氏综合症患者（非DS-AMKL）的AMKL发育。为了比较DS-AMKL和非DS-AMKL的BLAST细胞的生物学特征，我们比较了来自AMKL的19名儿童的BLAST细胞中造血转录因子的表达（DS-AMKL：11，非DS-AMKL：NON-DS-AMKL：9）。爆炸细胞的形态分为四组：1型，完全统一的爆炸； 2型，与细胞质泡沫中间分化的爆炸； 3型，用肌除毛细胞增生的爆炸； 4型，具有深蓝色细胞质的爆炸。为了按分子水平定义分化阶段，我们量化了与巨核 - 雌性细胞谱系相关的转录因子的表达。 GATA1，GATA2，FOG-1，NF-E2，SCL，PU.1，C/EBPα，C-MPL，EPO-R，CD41B，βGlobin。总之，DS-AMKL的爆炸不仅分化为巨核细胞，而且分化为毛磷脂A和βGlobin在GATA1基因突变下的过表达，因此分化为红细胞谱系。除非非DS-AMKL考虑基因改变和转录因子水平的完全不同的模式，否则应将DS-AMKL分为其他类别。