Lim Alvin S T, Krishnan Sathish, Lim Tse Hui, See Karen, Ng Yit Jun, Tan Yu Min, Choo Natasha, Lau Lai Ching, Tien Sim Leng, Ma Jun, Tan Daryl
Cytogenetics Laboratory, Department of Pathology, Singapore General Hospital, The Academia-Diagnostics Tower, L9, 20 College Road, Singapore, 169856 Singapore.
Department of Haematology, Singapore General Hospital, Singapore, Singapore.
Indian J Hematol Blood Transfus. 2014 Dec;30(4):253-8. doi: 10.1007/s12288-013-0294-8. Epub 2013 Sep 4.
Much effort has been made to stratify multiple myeloma patients for targeted therapy. However, responses have been varied and improved patient stratifications are needed. Forty-five diagnostic samples from multiple myeloma patients (median age 65 years) were stratified cytogenetically as 15 having non-hyperdiploidy, 20 having hyperdiploidy and 10 having a normal karyotype. Fluorescence in situ hybridization (FISH) assays with FGFR3/IGH, CCND1/IGH, IGH/MAF, RB1 and TP53 probes on bone marrow samples showed that IGH rearrangements were the most common abnormality in the non-hyperdiploid group but these were also found among hyperdiploid patients and patients with normal cytogenetics. Of these, FGFR3/IGH rearrangements were most frequent. Deletion of RB1/monosomy 13 was the most common genetic abnormality across the three groups and was significantly higher among non-hyperdiploid compared to hyperdiploid patients. On the other hand, the study recorded a low incidence of TP53 deletion/monosomy 17. The FGFR3/IGH fusion was frequently seen with RB1 deletion/monosomy 13. FISH with 1p36/1q21 and 6q21/15q22 probes showed that amplification of 15q22 was seen in all of the hyperdiploid patients while amplification of 1q21, Amp(1q21), characterized non-hyperdiploid patients. In contrast, deletions of 1p36 and 6q21 were very rare events. Amp(1q21), FGFR3/IGH fusion, RB1 deletion/monosomy 13, and even TP53 deletion/monosomy 17 were seen in some hyperdiploid patients, suggesting that they have a less than favorable prognosis and require closer monitoring.
为使多发性骨髓瘤患者能够接受靶向治疗,人们付出了诸多努力。然而,治疗反应各异,仍需改进患者分层方法。对45例多发性骨髓瘤患者(中位年龄65岁)的诊断样本进行细胞遗传学分层,其中15例为非超二倍体,20例为超二倍体,10例核型正常。对骨髓样本进行FGFR3/IGH、CCND1/IGH、IGH/MAF、RB1和TP53探针的荧光原位杂交(FISH)检测,结果显示IGH重排在非超二倍体组中是最常见的异常,但在超二倍体患者和细胞遗传学正常的患者中也有发现。其中,FGFR3/IGH重排最为频繁。RB1缺失/13号染色体单体性是三组中最常见的基因异常,在非超二倍体患者中的发生率显著高于超二倍体患者。另一方面,该研究记录的TP53缺失/17号染色体单体性发生率较低。FGFR3/IGH融合常与RB1缺失/13号染色体单体性同时出现。使用1p36/1q21和6q21/15q22探针进行FISH检测显示,所有超二倍体患者均出现15q22扩增,而1q21扩增(Amp(1q21))则为非超二倍体患者的特征。相比之下,1p36和6q21缺失是非常罕见的情况。在一些超二倍体患者中也发现了Amp(1q21)、FGFR3/IGH融合、RB1缺失/13号染色体单体性,甚至TP53缺失/17号染色体单体性,这表明这些患者预后不佳,需要密切监测。