Manfioletti G, Gattei V, Buratti E, Rustighi A, De Iuliis A, Aldinucci D, Goodwin G H, Pinto A
Dipartimento di Biochimica, Biofisica Chimica delle Macromolecole, Università di Trieste, Italy.
Blood. 1995 Mar 1;85(5):1237-45.
Proline-rich homeobox (Prh) is a novel human homeobox-containing gene recently isolated from the CD34+ cell line KG-1A, and whose expression appears mainly restricted to hematopoietic tissues. To define the pattern of Prh expression within the human hematopoietic system, we have analyzed its constitutive expression in purified cells obtained from normal hematopoietic tissues, its levels of transcription in a number of leukemia/lymphoma cell lines representing different lineages and stages of hematolymphopoietic differentiation, and its regulation during in vitro maturation of human leukemic cell lines. Prh transcripts were not detected in leukemic cells of T-lymphoid lineage, irrespective of their maturation stage, and in resting or activated normal T cells from peripheral blood and lymphoid tissues. In contrast, high levels of Prh expression were shown in cells representing early stages of B lymphoid maturation, being maintained up to the level of circulating and tissue mature B cells. Terminal B-cell differentiation appeared to be conversely associated with the deactivation of the gene, since preplasmacytic and plasmocytoma cell lines were found not to express Prh mRNA. Prh transcripts were also shown in human cell lines of early myelomonocytic, erythromegakaryocytic, and preosteoclast phenotypes. Prh expression was lost upon in vitro differentiation of leukemic cell lines into mature monocyte-macrophages and megakaryocytes, whereas it was maintained or upregulated after induction of maturation to granulocytes and osteoclasts. Accordingly, circulating normal monocytes did not display Prh mRNA, which was conversely detected at high levels in purified normal granulocytes. Our data, which show that the acquisition of the differentiated phenotype is associated to Prh downregulation in certain hematopoietic cells but not in others, also suggest that a dysregulated expression of this gene might contribute to the process of leukemogenesis within specific cell lineages.
富含脯氨酸的同源盒基因（Prh）是一种新的含人类同源盒基因，最近从CD34+细胞系KG-1A中分离出来，其表达似乎主要局限于造血组织。为了确定Prh在人类造血系统中的表达模式，我们分析了其在从正常造血组织获得的纯化细胞中的组成性表达、在代表造血淋巴细胞分化不同谱系和阶段的多种白血病/淋巴瘤细胞系中的转录水平，以及其在人类白血病细胞系体外成熟过程中的调控情况。在T淋巴细胞谱系的白血病细胞中未检测到Prh转录本，无论其成熟阶段如何，在外周血和淋巴组织中的静止或活化正常T细胞中也未检测到。相反，在代表B淋巴细胞成熟早期阶段的细胞中显示出高水平的Prh表达，这种表达一直维持到循环和组织成熟B细胞水平。终末B细胞分化似乎与该基因的失活相反相关，因为发现前浆细胞和浆细胞瘤细胞系不表达Prh mRNA。Prh转录本也在早期髓单核细胞、红巨核细胞和破骨细胞前体细胞系中显示。白血病细胞系体外分化为成熟单核细胞-巨噬细胞和巨核细胞后，Prh表达消失，而诱导成熟为粒细胞和破骨细胞后，Prh表达维持或上调。因此，循环正常单核细胞不显示Prh mRNA，相反，在纯化的正常粒细胞中检测到高水平的Prh mRNA。我们的数据表明，在某些造血细胞中获得分化表型与Prh下调相关，但在其他细胞中并非如此，这也表明该基因的表达失调可能有助于特定细胞谱系内的白血病发生过程。
