Sahota S S, Leo R, Hamblin T J, Stevenson F K
Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals, Southampton, UK.
Blood. 1996 Jan 15;87(2):746-55.
Plasma cell tumors display a wide spectrum of clinical progression, ranging from aggressive multiple myeloma to a benign form known as monoclonal gammopathy of undetermined significance (MGUS), which requires no treatment. Because both diseases involve mature Ig-secreting plasma cells, the reason for this variation in malignant behavior is unclear. However, assessment of malignant potential is desirable for choice of treatment protocols. Ig variable (VH) gene sequences analysis has previously shown the tumor cell of multiple myeloma to be postfollicular, with mutated homogeneous clonal sequences indicating no continuing exposure to the somatic hypermutation mechanism, and this was confirmed in 7 of 7 patients. Comparison of the VH gene sequences in the monoclonal cells in MGUS yielded a different result, with 3 of 7 patients demonstrating mutated heterogeneous sequences consistent with the tumor cells remaining under the influence of the mutator. In 1 of 3 of these patients, an IgM-positive precursor cell was identified that expressed heterogeneous VH sequences similar to those of the isotype-switched plasma cell. These results indicate that the clonal cells in MGUS differ from those in myeloma and suggest that the difference may reflect malignant potential.
浆细胞肿瘤表现出广泛的临床进展范围，从侵袭性多发性骨髓瘤到一种称为意义未明的单克隆丙种球蛋白病（MGUS）的良性形式，后者无需治疗。由于这两种疾病都涉及分泌Ig的成熟浆细胞，这种恶性行为差异的原因尚不清楚。然而，评估恶性潜能对于治疗方案的选择是可取的。Ig可变区（VH）基因序列分析先前已表明多发性骨髓瘤的肿瘤细胞位于滤泡后，其突变的同源克隆序列表明不再持续暴露于体细胞超突变机制，并且在7名患者中的7例得到了证实。对MGUS中单克隆细胞的VH基因序列进行比较得出了不同的结果，7名患者中有3例显示出突变的异源序列，这与肿瘤细胞仍受突变体影响一致。在这3名患者中的1例中，鉴定出一个IgM阳性前体细胞，其表达的异源VH序列与同种型转换浆细胞的序列相似。这些结果表明MGUS中的克隆细胞与骨髓瘤中的克隆细胞不同，并表明这种差异可能反映了恶性潜能。
