Koren-Michowitz Maya, Hardan Izhar, Berghoff Janina, Yshoev Galina, Amariglio Ninette, Rechavi Gideon, Nagler Arnon, Trakhtenbrot Luba
Division of Hematology, The Sheba Cancer Research Center, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Cancer Lett. 2007 Oct 8;255(2):307-14. doi: 10.1016/j.canlet.2007.05.005. Epub 2007 Jun 27.
Ploidy status and chromosomal aberrations involving chromosome 13q and the immunoglobulin heavy chain locus (IgH) are important prognostic features in multiple myeloma (MM). However, conventional cytogenetic studies are often not reveling and determination of plasma cells (PC) ploidy status in MM is technically difficult. We have used a combined cell morphology and interphase FISH (I-FISH) analysis in 184 consecutive BM samples from 136 MM patients for the diagnosis of chromosome 13q deletion [del (13q)] and IgH abnormalities. We have found a high prevalence (37%) of near-tetraploid (NT) PC in the BM samples studied. NT status of PC was verified with DNA index (DI) measurements. del (13q) was found in 69% and a total absence of one IgH copy (loss of IgH) in 20% of NT samples. We have shown that the presence of del (13q) and loss of IgH can be masked in NT cases: in 12 NT samples originally identified as normal for del (13q) the abnormality was obscured in the majority of plasma cells due to the presence of NT. Similarly, loss of IgH was masked in four samples with a large population of NT cells. Moreover, in one case the appearance of a 100% tetraploidy during disease progression masked the presence of del (13q), originally present, and could therefore falsely appear as disappearance of this prognostic marker. In conclusion, we have shown that a combination of three abnormalities, i.e., del (13q), loss of IgH and NT, all of potential prognostic significance, can be overlooked unless NT is specifically searched for and ruled out. Therefore, we suggest that a search for NT should be added to the routine BM assessment in MM patients.
倍性状态以及涉及13号染色体长臂（13q）和免疫球蛋白重链基因座（IgH）的染色体畸变是多发性骨髓瘤（MM）重要的预后特征。然而，传统的细胞遗传学研究往往无法揭示相关信息，并且在MM中确定浆细胞（PC）的倍性状态在技术上存在困难。我们对136例MM患者的184份连续骨髓样本进行了细胞形态学和间期荧光原位杂交（I-FISH）分析相结合的方法，以诊断13号染色体长臂缺失[del(13q)]和IgH异常。我们发现，在所研究的骨髓样本中，近四倍体（NT）PC的发生率很高（37%）。通过DNA指数（DI）测量验证了PC的NT状态。在69%的样本中发现了del(13q)，在20%的NT样本中完全缺失一个IgH拷贝（IgH缺失）。我们已经表明，del(13q)的存在和IgH的缺失在NT病例中可能被掩盖：在最初被鉴定为del(13q)正常的12个NT样本中，由于NT的存在，大多数浆细胞中的异常被掩盖。同样，在四个含有大量NT细胞的样本中，IgH的缺失也被掩盖。此外，在一个病例中，疾病进展过程中100%四倍体的出现掩盖了最初存在的del(13q)的存在，因此可能错误地显示为该预后标志物的消失。总之，我们已经表明，三种异常情况，即del(13q)、IgH缺失和NT，所有这些都具有潜在的预后意义，除非专门寻找并排除NT，否则可能会被忽视。因此，我们建议在MM患者的常规骨髓评估中增加对NT的检测。
