Jadayel D, Calabrese G, Min T, van Rhee F, Swansbury G J, Dyer M J, Maitland J, Palka G, Catovsky D
Academic Department of Haematology and Cytogenetics, Institute of Cancer Research/Royal Marsden Hospital, Surrey, UK.
Leukemia. 1995 Jun;9(6):981-7.
We report the molecular cytogenetic analysis of a case of Philadelphia (Ph)-negative, BCR-positive chronic myeloid leukemia (CML) which appeared by conventional cytogenetics to have a t(6;9)(p23;q34) as the sole cytogenetic abnormality. Neither conventional nor pulse-field Southern blots detected any rearrangement of the DEK or CAN genes which are often fused in acute myeloid leukemia (AML) with t(6;9)(p23;q34). However, rearrangements of both BCR and ABL genes were detected. The breakpoint in BCR was located in the major translocation cluster region between exons b1 and b3. ABL rearrangements were detected with an ABL exon 1B probe and with a probe located 5' of the entire ABL gene. Comigration between the rearranged fragments obtained with M-bcr-5' and ABL exon 1B probes was observed, implying that the entire ABL gene was fused to the 5' part of the BCR gene. Fluorescence in situ hybridization (FISH) analyses using BCR and ABL probes showed that in 20% of metaphases BCR and ABL signals were present on one chromosome 6 at 6p23, whilst in 80% of metaphases BCR and ABL signals were identified on both copies of chromosome 6. Furthermore, FISH analysis with a whole-chromosome 22 paint demonstrated that chromosome 22 material was present on both copies of chromosome 6. These data indicate a complex Philadelphia translocation involving chromosome band 6p23 and duplication of the whole aberrant chromosome. The nature of the gene locus on 6p23, involved in this rearrangement, remains unknown. A similar translocation has been previously reported in a case of CML, which also lacked DEK and CAN gene rearrangements implying that abnormalities of 6p23 involving genes other than DEK may be a recurrent abnormality in CML.
我们报告了一例费城（Ph）阴性、BCR阳性慢性髓性白血病（CML）的分子细胞遗传学分析。常规细胞遗传学显示，该病例唯一的细胞遗传学异常为t(6;9)(p23;q34)。无论是常规Southern印迹还是脉冲场Southern印迹，均未检测到DEK或CAN基因的任何重排，这两个基因在急性髓性白血病（AML）伴t(6;9)(p23;q34)时经常发生融合。然而，检测到了BCR和ABL基因的重排。BCR的断点位于外显子b1和b3之间的主要易位簇区域。使用ABL外显子1B探针和位于整个ABL基因5'端的探针检测到ABL重排。观察到用M-bcr-5'和ABL外显子1B探针获得的重排片段共迁移，这意味着整个ABL基因与BCR基因的5'部分融合。使用BCR和ABL探针的荧光原位杂交（FISH）分析显示，在20%的中期相中，BCR和ABL信号出现在6号染色体6p23的一条染色体上，而在80%的中期相中，BCR和ABL信号在6号染色体的两个拷贝上均被识别。此外，用全染色体22探针进行的FISH分析表明，6号染色体的两个拷贝上均存在22号染色体物质。这些数据表明存在涉及6p23染色体带的复杂费城易位以及整个异常染色体的重复。参与这种重排的6p23上基因位点的性质仍然未知。先前在一例CML病例中也报道了类似的易位，该病例也缺乏DEK和CAN基因重排，这意味着涉及DEK以外基因的6p23异常可能是CML中的一种复发性异常。
