Gene expression of hematopoietic transcription factors in pediatric acute megakaryocytic leukemia

急性巨核细胞白血病(AMKL)具有不同的异质性，包括形态学和细胞遗传学研究。在儿童中，已描述了两个主要亚型：唐氏综合征患者发生的AMKL(DS-AMKL)和非唐氏综合征患者的AMKL(非DS-AMKL)。为了比较DS-AMKL和非DS-AMKL原始细胞的生物学特性，我们比较了19例AMKL(DS-AMKL：11，非DS-AMKL：9)原始细胞中造血转录因子的表达。原始细胞的形态可分为四组：类型1，完全未分化的原始细胞；类型2，胞浆中分化的原始细胞；类型3，巨核生成障碍的原始细胞；类型4，胞浆深蓝色的原始细胞。为了从分子水平确定分化阶段，我们定量了与巨核红系细胞系相关的转录因子的表达：GATA1、GATA2、FOG-1、NF-E2、Sc1、PU.1、C/EBPα、c-MPL、EPO-R、CD41b、β珠蛋白。总之，在GATA1基因突变下，由于糖蛋白A和β珠蛋白的过度表达，DS-AMKL的原始细胞不仅分化为巨核细胞，而且还分化为红系。考虑到基因改变和转录因子水平的完全不同，DS-AMKL应该被归类为非DS-AMKL以外的其他类别。

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.