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额外染色体改变在多发性骨髓瘤中t(4;14)和del(17p)预后价值中的作用:IFM研究经验

Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience.

作者信息

Hebraud Benjamin, Magrangeas Florence, Cleynen Alice, Lauwers-Cances Valerie, Chretien Marie-Lorraine, Hulin Cyrille, Leleu Xavier, Yon Edwige, Marit Gerald, Karlin Lionel, Roussel Murielle, Stoppa Anne-Marie, Belhadj Karim, Voillat Laurent, Garderet Laurent, Macro Margaret, Caillot Denis, Mohty Mohamad, Facon Thierry, Moreau Philippe, Attal Michel, Munshi Nikhil, Corre Jill, Minvielle Stephane, Avet-Loiseau Herve

机构信息

Laboratory for Genomics in Myeloma, Institut Universitaire du Cancer and University Hospital, Toulouse, France; Centre de Recherche en Cancérologie de Toulouse INSERM U1037, Toulouse, France;

Unité Mixte de Génomique du Cancer, University Hospital, Nantes, France; INSERM U892, Nantes, France;

出版信息

Blood. 2015 Mar 26;125(13):2095-100. doi: 10.1182/blood-2014-07-587964. Epub 2015 Jan 30.

Abstract

In multiple myeloma, cytogenetic changes are important predictors of patient outcome. In this setting, the most important changes are deletion 17p, del(17p), and translocation of chromosomes 4 and 14, t(4;14), conferring a poor outcome. However, a certain degree of heterogeneity is observed in the survival of these high-risk patients. We hypothesized that other chromosomal changes may impact the outcome. We retrospectively analyzed a large series of 242 patients displaying either t(4;14) (157 patients) or del(17p) (110 patients), 25 patients presenting both abnormalities, using single nucleotide polymorphism array. In patients with t(4;14), del(1p32), del22q, and >30 chromosomal structural changes negatively impacted progression-free survival (PFS). For overall survival (OS), del(13q14), del(1p32), and the number of chromosomal structural changes worsened the prognosis of patients. For patients with del(17p), del6q worsened the prognosis of patients, whereas trisomy 15 and monosomy 14 were found to have a protective effect on PFS. For OS, del(1p32) worsened the prognosis of patients, whereas having >8 numerical changes was found to have a protective effect on survival. This study, which is the largest series of high-risk patients analyzed with the most modern genomic technique, identified 1 main factor negatively impacting survival: del(1p32).

摘要

在多发性骨髓瘤中,细胞遗传学改变是患者预后的重要预测指标。在这种情况下,最重要的改变是17p缺失(del(17p))以及4号和14号染色体易位(t(4;14)),这些改变预示着不良预后。然而,在这些高危患者的生存情况中观察到了一定程度的异质性。我们推测其他染色体改变可能会影响预后。我们使用单核苷酸多态性阵列对一大组242例患者进行了回顾性分析,这些患者要么存在t(4;14)(157例),要么存在del(17p)(110例),25例患者同时存在这两种异常。在伴有t(4;14)的患者中,1p32缺失、22q缺失以及超过30种染色体结构改变对无进展生存期(PFS)产生负面影响。对于总生存期(OS),13q14缺失、1p32缺失以及染色体结构改变的数量使患者预后变差。对于伴有del(17p)的患者,6q缺失使患者预后变差,而15号染色体三体和14号染色体单体对PFS具有保护作用。对于OS,1p32缺失使患者预后变差,而存在超过8种数量改变对生存具有保护作用。这项研究是使用最现代基因组技术分析高危患者的最大系列研究,确定了1个对生存产生负面影响的主要因素:1p32缺失。

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