Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with total therapy I: interpretation in the context of global gene expression
Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with total therapy I: interpretation in the context of global gene expression
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DOI：
10.1182/blood-2002-09-2873
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发表时间：
2003-05-15
期刊：
影响因子：
20.3
通讯作者：
Barlogie, B
中科院分区：
文献类型：
--
作者：
Shaughnessy, J;Jacobson, J;Barlogie, B
中期细胞遗传学异常（CAs），特别是13号染色体异常（ca13），即使在总治疗1中应用了串联自体移植，也会给多发性骨髓瘤患者带来严重的预后，总治疗1在1989年至1994年期间纳入了231例患者。中位随访时间近9年，研究了治疗前和复发时检测到的所有个体ca的预后影响。在治疗前检查的所有CA和标准预后因素中，只有低二倍体和CA 13（低-13 CA）单独或联合与最短无事件生存期和总生存期（OS）相关。复发后最短的OS是低-13 CA，在所有28例复发时出现这种异常的患者中有18例新发现。良好的预后与诊断和复发时没有任何CA相关（10年OS， 40%）。其他CA缺乏独立的预后意义，表明低-13 CA具有独特的侵袭性行为（在诊断时存在于16%的患者中）。在总疗法11的146例患者中使用微阵列数据，细胞周期基因的过表达将CA与无CA区分开来，特别是在通过间期荧光原位杂交（FISH）检测到del（l3）的情况下。FISH 13导致RB1和其他13号染色体上的基因单倍体不足，以及IGF1R的激活，似乎对细胞周期基因表达有放大作用，从而为CA 13患者与其他CA患者相比的可怕结局提供了分子解释。(C) 2003年由美国血液病学会出版。
Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy 1, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo-13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo-13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo-13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy 11, over-expression of cell cycle genes distinguished CA from no CA, especially in cases of del(l 3) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs. (C) 2003 by The American Society of Hematology.