In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression
In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression
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DOI：
10.1182/blood-2002-06-1675
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发表时间：
2003-02-15
期刊：
影响因子：
20.3
通讯作者：
Pilarski, LM
中科院分区：
文献类型：
--
作者：
Keats, JJ;Reiman, T;Pilarski, LM
本研究分析了1994年至2001年诊断的208例多发性骨髓瘤（MM）患者和52例意义不明的单克隆丙种球蛋白病（MGUS）患者中t（4;14）（p16;q32）的频率和临床意义。采用逆转录-聚合酶链反应（RTPCR）检测der（4）染色体上的混合免疫球蛋白重链（IgH）-MMSET转录本，以确定易位患者。我们发现31例（14.9%）t（4;14）（+）MM患者和1例（1.9%）t（4;14）（+）- MGUS患者。在骨髓（BM）和血液中检测IgH-MMSET杂交转录物。断点分析显示，67.7%的t（4;14）（+）患者表达可能编码全长MMSET的杂交转录本，而其余患者缺乏一个或多个氨基末端外显子。31例t（4;14）（+）MM患者中仅23例（74%）通过RT-PCR检测到成纤维细胞生长因子受体3（FGFR 3）表达，推测为der（14）失调。对53例多发骨髓和血液样本的MM患者的纵向分析显示，随着时间的推移，t（4;14）（+）患者的骨髓保持阳性，t（4;14）（+）患者未获得易位。IgH-MMSET杂合转录物和FGFR 3转录物在对治疗的应答期间从血液中消失。t（4;14）的发生与已知的预后指标之间没有相关性。然而，我们发现t（4;14）易位预测生存率低（P = 0.006;中位数，644天vs 1288天;风险比[HR]，2.0），即使在FGFR 3非表达者中也是如此（P = 0.003）。t（4;14）的存在也预示着一线化疗反应不良（P = .05）。这些结果表明MM中t（4;14）易位的显著临床影响，其独立于FGFR 3表达。(C)2003年，美国血液学会。
This study analyzed the frequency and clinical significance of t(4;14)(p16;q32) in multiple myeloma (MM) among 208 patients with MM and 52 patients with monoclonal gammopathy of undetermined significance (MGUS); diagnosed between 1994 and 2001. Patients with the translocation were identified using reverse transcription-polymerase chain reaction (RTPCR) to detect hybrid immunoglobulin heavy chain (IgH)-MMSET transcripts from the der(4) chromosome. We found 31 (14.9%) t(4;14)(+) MM patients and 1 (1.9%)t(4;14)(+)- MGUS patient. IgH-MMSET hybrid transcripts were detected in bone marrow (BM) and blood. Breakpoint analysis revealed that 67.7% of t(4;14)(+) patients expressed hybrid transcripts potentially encoding full-length MMSET, whereas the remainder lacked one or more amino terminal exons. Expression of fibroblast growth factor receptor 3 (FGFR3), presumptively dysregulated on der(14), was detected by RT-PCR in only 23 of 31 (74%) patients with t(4;14)(+) MM. Patients lacking FGFR3 expression also lacked detectable der(l 4) products. Longitudinal analysis of 53 MM patients with multiple BM and blood samples showed that, over time, BM from t(4;14)(+) patients remained positive and that t(4;14)(+) patients did not acquire the translocation. IgH-MMSET hybrid transcripts and FGFR3 transcripts disappeared from blood during response to therapy. No correlation was observed between the occurrence of t(4;14) and known prognostic indicators. However, we find the t(4;14) translocation predicts for poor survival (P = .006; median, 644 days vs 1288 days; hazard ratio [HR], 2.0), even in FGFR3 nonexpressors (P = .003). The presence of t(4;14) is also predictive of poor response to first-line chemotherapy (P = .05). These results indicate a significant clinical impact of the t(4;14) translocation in MM that is independent of FGFR3 expression. (C) 2003 by The American Society of Hematology.