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异基因骨髓移植后的供者白血病

Donor leukemia following allogeneic bone marrow transplantation.

作者信息

Mc Cann S R, Lawler M, Gardiner N, O'Riordan J, Humphries P, De Arce M

机构信息

Department of Haematology, St. James's Hospital, Dublin, Ireland.

出版信息

Leukemia. 1994 Apr;8 Suppl 1:S133-5.

PMID:8152280
Abstract

Although allogeneic bone marrow transplantation has been shown to be a highly effective treatment for acute and chronic leukemia, leukemic relapse remains a significant problem. Leukemic relapse occurs in recipient cells in the majority of cases, but the paucity of donor cell leukemias may reflect the sensitivity of the investigative technique. We have developed a highly sensitive technique to identify the origin of all hematopoietic cells in the post transplant state which is based on PCR amplification of microsatellites, polymorphic tandem repetitive elements. We have identified donor leukemia (AML M5) following a sex matched BMT for severe aplastic anemia, verified a previously reported case of donor leukemia following BMT for chronic granulocytic leukemia and recently identified an acquired cytogenetic abnormality(del 11q23) in donor cells four years following an apparently successful BMT for AML. In all cases the donors have remained healthy. Postulated mechanisms include transfer to the transplanted marrow of a dormant oncogene residing in the DNA of either a virus, the chromosomes of degenerating irradiation damaged host leukemic cells or in the marrow stroma which is radioresistant and host in origin following BMT. Using sensitive techniques donor leukemia has been shown to be a more common event than was previously thought and an understanding of its pathogenesis may allow us to elucidate leukemogenic mechanisms in man.

摘要

尽管同种异体骨髓移植已被证明是治疗急性和慢性白血病的一种高效疗法,但白血病复发仍然是一个重大问题。在大多数情况下,白血病复发发生在受体细胞中,但供体细胞白血病病例较少可能反映了检测技术的敏感性。我们开发了一种高度敏感的技术,用于识别移植后状态下所有造血细胞的来源,该技术基于微卫星(多态性串联重复元件)的PCR扩增。我们在一名严重再生障碍性贫血患者接受性别匹配的骨髓移植后发现了供体白血病(AML M5),证实了之前报道的一例慢性粒细胞白血病患者骨髓移植后发生供体白血病的病例,并且最近在一名急性髓系白血病患者接受明显成功的骨髓移植四年后,在供体细胞中发现了一种获得性细胞遗传学异常(11q23缺失)。在所有这些病例中,供体一直保持健康。推测的机制包括将存在于病毒DNA、退化的受辐射损伤宿主白血病细胞染色体或骨髓基质中的休眠致癌基因转移到移植的骨髓中,骨髓基质在骨髓移植后具有放射抗性且源自宿主。使用敏感技术已表明,供体白血病是比之前认为的更常见的事件,对其发病机制的理解可能使我们能够阐明人类白血病发生机制。

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