Fonseca Rafael, Blood Emily A, Oken Martin M, Kyle Robert A, Dewald Gordon W, Bailey Richard J, Van Wier Scott A, Henderson Kimberly J, Hoyer James D, Harrington David, Kay Neil E, Van Ness Brian, Greipp Philip R
Mayo Clinic Department of Hematology and Internal Medicine, Minneapolis, MN 55905, USA.
Blood. 2002 May 15;99(10):3735-41. doi: 10.1182/blood.v99.10.3735.
The t(11;14)(q13;q32) results in up-regulation of cyclin D1 and is the most common translocation detected in multiple myeloma, where it is also associated with a lymphoplasmacytic morphology. We performed an interphase fluorescent in situ hybridization (FISH) study to determine the clinical and biologic significance of the abnormality when testing a large cohort of myeloma patients. Bone marrow slides from multiple myeloma patients entered into the Eastern Cooperative Oncology Group phase III clinical trial E9486 and associated laboratory correlative study E9487 were analyzed using interphase FISH combined with immune-fluorescent (cytoplasmic immunoglobulin-FISH) detection of clonal plasma cells. We used FISH probes that hybridize to the 14q32 and 11q13 chromosomal loci. The t(11;14)(q13;q32) was correlated with known biologic and prognostic factors. Of 336 evaluable patients, 53 (16%) had abnormal FISH patterns compatible with the t(11;14)(q13;q32). These patients appeared to be more likely to have a serum monoclonal protein of less than 10 g/L (1 g/dL) (28% vs 15%, P =.029) and a lower plasma cell labeling index (P =.09). More strikingly, patients were less likely to be hyperdiploid by DNA content analysis (n = 251, 14% vs 62%, P <.001). Patients with the t(11;14)(q13;q32) appeared to have better survival and response to treatment, although this did not reach statistical significance. Multiple myeloma with the t(11;14)(q13;q32) is a unique subset of patients, not only characterized by cyclin D1 up-regulation and a lymphoplasmacytic morphology, but is also more frequently associated with small serum monoclonal proteins and is much less likely to be hyperdiploid. These patients do not have a worsened prognosis as previously thought.
t(11;14)(q13;q32)导致细胞周期蛋白D1上调，是在多发性骨髓瘤中检测到的最常见的易位，在该病中它还与淋巴浆细胞形态相关。我们进行了一项间期荧光原位杂交（FISH）研究，以确定在检测一大群骨髓瘤患者时该异常的临床和生物学意义。使用间期FISH结合免疫荧光（细胞质免疫球蛋白-FISH）检测克隆浆细胞，对进入东部肿瘤协作组III期临床试验E9486和相关实验室相关性研究E9487的多发性骨髓瘤患者的骨髓涂片进行了分析。我们使用了与14q32和11q13染色体位点杂交的FISH探针。t(11;14)(q13;q32)与已知的生物学和预后因素相关。在336例可评估患者中，53例（16%）的FISH模式异常，与t(11;14)(q13;q32)相符。这些患者似乎更有可能血清单克隆蛋白低于10 g/L（1 g/dL）（28%对15%，P = 0.029）且浆细胞标记指数较低（P = 0.09）。更显著的是，通过DNA含量分析，这些患者超二倍体的可能性较小（n = 251，14%对62%，P < 0.001）。尽管未达到统计学意义，但具有t(11;14)(q13;q32)的患者似乎有更好的生存率和对治疗的反应。伴有t(11;14)(q13;q32)的多发性骨髓瘤是一个独特的患者亚组，不仅以细胞周期蛋白D1上调和淋巴浆细胞形态为特征，而且更常与血清小单克隆蛋白相关，且超二倍体的可能性要小得多。这些患者的预后并不像之前认为的那样差。
