Boultwood J, Fidler C, Lewis S, MacCarthy A, Sheridan H, Kelly S, Oscier D, Buckle V J, Wainscoat J S
Department of Haematology, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Blood. 1993 Nov 1;82(9):2611-6.
Acquired interstitial deletions of the long arm of chromosome 5 occur frequently in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Recently IRF1, a putative tumor suppressor gene localized to the long arm of chromosome 5, has been shown to be deleted from the 5q- chromosome in a group of patients with MDS and AML. It has been suggested that the loss of IRF1 may be critical to the development of the 5q- syndrome. We have investigated the allelic loss of IRF1 in a group of 12 patients with MDS and a 5q deletion and 2 patients with AML and a 5q deletion. Gene dosage experiments demonstrated that 12 of 14 patients had loss of one allele of the IRF1 gene but no evidence of homozygous loss and that 2 patients with 5q- syndrome retained both copies of the gene. The retention of IRF1 on the 5q- chromosome in these two cases has been confirmed by fluorescent in situ hybridization localization using an IRF1 cosmid. Pulsed field gel electrophoresis was used to determine whether there was any evidence for structural rearrangement in the region encompassing the IRF1 gene in these two patients. No aberrant bands were detected with a range of rare cutter enzyme digests. We conclude that IRF1 maps outside the commonly deleted segment of the 5q- chromosome and that loss of IRF1 is not solely responsible for the development of the 5q- syndrome.
5号染色体长臂的获得性间质缺失在骨髓增生异常综合征（MDS）和急性髓系白血病（AML）中频繁出现。最近，定位于5号染色体长臂的一个假定的肿瘤抑制基因IRF1，在一组MDS和AML患者中被发现从5q-染色体上缺失。有人提出，IRF1的缺失可能对5q-综合征的发生至关重要。我们研究了一组12例伴有5q缺失的MDS患者和2例伴有5q缺失的AML患者中IRF1的等位基因缺失情况。基因剂量实验表明，14例患者中有12例IRF1基因的一个等位基因缺失，但没有纯合缺失的证据，并且2例5q-综合征患者保留了该基因的两个拷贝。通过使用IRF1黏粒进行荧光原位杂交定位，证实了这两例患者的5q-染色体上保留了IRF1。脉冲场凝胶电泳用于确定这两名患者中包含IRF1基因的区域是否有结构重排的证据。使用一系列稀有切割酶消化未检测到异常条带。我们得出结论，IRF1定位于5q-染色体常见缺失区段之外，并且IRF1的缺失并非5q-综合征发生的唯一原因。
