CHARACTERISTIC PATTERNS OF HOX GENE-EXPRESSION IN DIFFERENT TYPES OF HUMAN LEUKEMIA
CHARACTERISTIC PATTERNS OF HOX GENE-EXPRESSION IN DIFFERENT TYPES OF HUMAN LEUKEMIA
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DOI：
10.1002/ijc.2910530211
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发表时间：
1993-01-21
影响因子：
6.4
通讯作者：
MAGLI, MC
中科院分区：
文献类型：
--
作者：
CELETTI, A;BARBA, P;MAGLI, MC
同源框基因是编码DNA结合蛋白的基因网络，在整个进化过程中高度保守。它们参与正常发育的控制以及成体分化系统中基因表达的调节，包括造血。近年来，含有同源异型盒基因的异常表达与白血病表型有关。人类HOX家族的同源异型盒基因被组织成4个大簇。我们分析了HOX基因在不同类型人类白血病中的表达，以探讨HOX基因的物理组织是否反映了参与造血细胞分化的调控等级，或者HOX基因的表达是否可能与白血病的表型有关。我们的结果表明，在髓系细胞中，HOX基因是协调调节的，而在淋巴系细胞中，它们似乎是作为孤立的基因发挥作用。在急性非淋巴细胞白血病中高表达的HOX2基因的6个相邻基因在慢性髓系白血病中被关闭，提示HOX2基因的下调可能是髓系细胞成熟所必需的。相反，一些分散的基因在淋巴组织中是活跃的。这些观察表明，造血细胞在特定的分化阶段表达一系列特定细胞系特有的HOX基因。HOX基因表达的特征模式可能反映了这些基因在正常和白血病造血过程中在细胞谱系确定中发挥的潜在重要作用。
Homeobox-containing genes are a network of genes encoding DNA-binding proteins highly conserved throughout evolution. They are involved in the control of normal development as well as in the regulation of gene expression in adult differentiating systems, including hematopoiesis. Aberrant expression of homeobox-containing genes has recently been related to leukemic phenotype. Human homeobox-containing genes of the HOX family are organized into 4 large clusters. We have analyzed the expression of HOX genes in different types of human leukemia to investigate whether the physical organization of HOX loci reflects a regulatory hierarchy involved in the differentiation of hematopoietic cells or whether HOX gene expression might contribute to the leukemic phenotype. Our results show that HOX genes are coordinately regulated in blocks in myeloid cells whereas they appear to function as isolated genes in lymphoid cells. Six contiguous genes of the HOX2 locus, highly expressed in acute non-lymphocytic leukemia, are switched off in chronic myelogenous leukemia, suggesting that down-regulation of HOX2 genes might be required for cell maturation of the myeloid lineages. In contrast, a few scattered genes are active in lymphoid populations. These observations suggest that hematopoietic cells express a repertoire of HOX genes characteristic of a particular cell lineage at a specific stage of differentiation. The characteristic patterns of HOX gene expression may reflect the potentially important role that these genes play in cell lineage determination during both normal and leukemic hematopoiesis.