Selleri L, Emilia G, Temperani P, Grassilli E, Zucchini P, Tagliafico E, Bonati A, Venezia L, Ferrari S, Torelli U
Institute of Internal Medicine and Hematology, University of Modena, Italy.
Leukemia. 1989 Jul;3(7):538-42.
Despite the major breakthrough in the knowledge of the molecular events underlying the t(9;22) translocation, still no consistent data have been found on the evolution of Ph1 positive CML from the chronic to the accelerated or blastic phase of the disease. In most patients in fact the bcr/abl rearrangements are identical both in chronic phase and in blast crisis, and overall differences in chronic phase duration, related to different location of breakpoints inside the bcr region, were found to be marginal. We approached this problem by studying the molecular features of the bcr/abl abnormality in rare CML patients with very long, atypical chronic phase. The three patients studied, whose chronic phase duration is 17, 19, and 21 years, respectively, have typical genomic bcr rearrangements, and two of them show, hybridizing Northern blots to c-abl, the 8.5 kb mRNA, as that typically present in CML. It seems that genomic alterations within bcr and abl cannot account, alone, for the duration of the chronic phase of Ph1 positive CML and those quantitative and/or qualitative alterations of the p210 bcr/abl protein, unluckily awkward to prove, might be responsible for the atypical clinical features of these CML long survivors.
尽管在t(9;22)易位所涉及的分子事件的认识上取得了重大突破，但关于Ph1阳性慢性粒细胞白血病（CML）从慢性期发展到加速期或急变期的过程，仍未找到一致的数据。事实上，在大多数患者中，bcr/abl重排在慢性期和急变期都是相同的，而且与bcr区域内断点位置不同相关的慢性期持续时间的总体差异被发现是微不足道的。我们通过研究罕见的具有非常长的非典型慢性期的CML患者中bcr/abl异常的分子特征来解决这个问题。所研究的三名患者，其慢性期持续时间分别为17年、19年和21年，具有典型的基因组bcr重排，其中两名患者在将Northern印迹与c-abl杂交时显示出8.5 kb的mRNA，这与CML中通常存在的情况相同。似乎bcr和abl内的基因组改变本身并不能解释Ph1阳性CML慢性期的持续时间，而p210 bcr/abl蛋白的那些定量和/或定性改变（不幸的是难以证实）可能是这些CML长期存活者非典型临床特征的原因。
