Chiecchio L, Protheroe R K M, Ibrahim A H, Cheung K L, Rudduck C, Dagrada G P, Cabanas E D, Parker T, Nightingale M, Wechalekar A, Orchard K H, Harrison C J, Cross N C P, Morgan G J, Ross F M
Leukaemia Research Fund UK Myeloma Forum Cytogenetics Group, Human Genetics Division, University of Southampton, Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts, UK.
Leukemia. 2006 Sep;20(9):1610-7. doi: 10.1038/sj.leu.2404304. Epub 2006 Jul 6.
In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (Delta13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n=794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if Delta13, p53 deletion or t(4;14) was present, but only Delta13 remained significant on multivariate analysis. Patients with Delta13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with Delta13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable Delta13 disappeared; their outcome matched that of patients with no detectable Delta13 (P=0.115). Addition of ploidy status to iFISH-Delta13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH Delta13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with Delta13. We conclude that Delta13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of Delta13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.
在骨髓瘤中,用于检测13号染色体缺失(Delta13)的不同策略的预后影响仍存在争议。为解决这一问题,我们在一项大型多中心研究(n = 794)中比较了传统细胞遗传学和间期荧光原位杂交(iFISH)。获得异常中期分裂相的能力与预后不良相关,如果存在Delta13、p53缺失或t(4;14),预后会更差,但在多变量分析中只有Delta13仍然具有显著意义。通过细胞遗传学或iFISH检测到Delta13的患者预后不良。然而,当将细胞遗传学和iFISH均可检测到Delta13的病例与仅通过iFISH检测到的病例分开时,iFISH可检测到的Delta13的不良预后消失了;他们的结局与未检测到Delta13的患者相当(P = 0.115)。将倍性状态添加到iFISH-Delta13中并不影响该检测的预后价值。实际上,细胞遗传学和iFISH Delta13均将超二倍体和非超二倍体分为两组,预后相似,这表明倍性的不良预后完全是由于其与Delta13相关。我们得出结论,中期分析检测到的Delta13是骨髓瘤的关键预后因素。即使在那些仅产生正常或无中期分裂相的患者中,Delta13的缺失也与相对较好的预后相关。