The role of newly cloned genes related to chromosome translocation on hematological differentiation and proliferation.

染色体易位在造血系统恶性肿瘤的发生中起重要作用。11 q13区域的研究为套细胞淋巴瘤的发病机制提供了新的线索，而11 q23区域的易位在各种类型的造血系统恶性肿瘤中反复出现。对于11 q13区域，我们通过对PRAD 1基因转录本和突变易位病例的断裂点区域的分析，证实了BCL-1与PRAD 1/cyclin D1基因的同源性。最近，我们生产了一种单克隆抗体，5D4，对PRAD 1/细胞周期蛋白D1的产品，并证明了特定的阳性核染色与套细胞淋巴瘤（MCL）。根据334例血液病患者的免疫组化资料， 关于我们 我们从11 q23区域克隆了两个基因，分别命名为MLL和PCK/P54基因。关于MLL基因，其编码与三胸果蝇同源的3969个氨基酸的多肽，包含由三个AT-钩基序和两个多锌指结构域组成的两个推定的DNA结合基序。急性白血病11 q23易位的断裂点几乎都位于MLL基因的簇区。我们建立了逆转录-聚合酶链反应（RT-PCR）。敏感性研究表明，在10^4至10^5个细胞中可以检测到具有嵌合mRNA的单个克隆。RUT-PER方法为11 q23易位白血病的诊断和治疗反应的监测提供了一种快速、准确、敏感的方法。我们在实验室培育了MLL转基因小鼠，并对其进行了一年半以上的观察。到目前为止，没有观察到荷瘤小鼠。少

Chromosome translocation has been demonstrated to play an important role in the genesis of hematopoietic malignancies. We focused the translocation involving the chromosome 11 band q13 and q23.Recent studies of 11q13 region have shed light on the pathogenesis of mantle cell lymphoma and the translocation on region 11q23 has been recurrently observed in various types of hematopoietic malignancies. Such as malignant lymphoma, acute promyelocytic leukemia, infantile leukemia and secondary leukemia occurring after chemotherapy.Regarding 11q13 region, we proved the identity between BCL-1 and the PRAD1/cyclin D1 gene based on our analyzes of the PRAD1 transcripts and the breakpoint region of the variant translocation case. Recently, we produced a monoclonal antibody, 5D4, against the PRAD1/cyclin D1 product and demonstrated specific positive nuclear staining to be associated with mantle cell lymphoma (MCL). According to the data of immunostaining obtained from 334 cases of hematological diso … More rders including 39 cases of MCL,the MCL showed the poorest prognosis among them.We cloned and characterize the two genes from the 11q23 region, and named MLL and PCK/P54 genes, respectively. Regarding MLL gene, which encodes a 3969 amino acid polypeptide homologous to Drosophila trithorax, containing two putative DNA-binding motifs consisting of three AT-hook motifs and two multiple zinc finger domains. Almost all the breakpoints in acute leukemia with 11q23 translocations lie in a cluster region on the MLL gene. We established the reverse trascriptase-polymerase chain reaction (RT-PCR). Sensitivity studies showed that a single clone with cheimeric mRNA in 10^4 to 10^5 cells could be detected. This RUT-PER method provide a rapid, accurate, and sensitive tool for diagnosing leukemia wtih 11q23 translocation and for monitoring response to therapy in these patients.Recent our analyzes of function of MLL gene show the data thate the N-terminal portion of this gene, may play an important role on tumorigeneses and differentiation. Furthermore we produced the MLL transgenic mice in our laboratory, we have observed them more than one and half year. No tumor bearing mouse was observed, so far. Less