The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q.
The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q.
复制标题
白细胞介素3基因位于人类5号染色体上，在髓性白血病中被删除，并伴有5q缺失。
DOI：
10.1073/pnas.84.16.5913
复制
发表时间：
1987
影响因子：
11.1
通讯作者：
Rowley,JD
中科院分区：
文献类型：
--
作者：
LeBeau,MM;Epstein,ND;O'Brien,SJ;Nienhuis,AW;Yang,YC;Clark,SC;Rowley,JD
IL-3基因编码白介素3，这是一种能够支持多种造血细胞增殖的造血细胞集落刺激因子(CSF)。通过体细胞杂交和染色体原位杂交，我们将该基因定位于人类5号染色体的q23-31带，这是一个在髓系疾病患者中经常缺失的染色体区域[del(5q)]。通过原位杂交，发现1例难治性贫血患者存在del(5)(q15q33.3)，3例难治性贫血(2例)或新发急性非淋巴细胞白血病(ANLL)患者有相似的远端断裂点[del(5)(q13q33.3)]，以及5例与治疗相关的ANLL患者，其Q33带远端断裂点相似[del(5)(q14q33.3)]，IL-3在5q染色体上缺失。对2例难治性贫血5q综合征患者保留正常或缺失5号染色体的体细胞杂交种的Southern杂交分析表明，保留5号染色体缺失的杂交种不存在IL-3序列，而具有细胞学正常5号染色体的杂交种则不存在IL-3序列。因此，5号染色体的一小段含有IL-3、GM-CSF(编码粒细胞-巨噬细胞-CSF的基因)、CSF-1(编码巨噬细胞-CSF的基因)和fms(编码CSF-1受体的人c-FMS原癌基因)。我们的发现和早期的结果表明，GM-CSF、CSF-1和FMS在5q染色体上缺失，提示IL-3或其他CSF基因的缺失可能在与del(5q)相关的血液病的发病机制中发挥重要作用。
The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, we localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33 [del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF (the gene encoding granulocyte-macrophage-CSF), CSF-1 (the gene encoding macrophage-CSF), and FMS (the human c-fms protooncogene, which encodes the CSF-1 receptor). Our findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).