Selleri L, Emilia G, Luppi M, Temperani P, Zucchini P, Tagliafico E, Artusi T, Sarti M, Donelli A, Castoldi G L
Institute of Internal Medicine and Hematology, University of Modena, Italy.
Hematol Pathol. 1990;4(2):67-77.
The Philadelphia (Ph1) chromosome is found in the majority of patients affected by chronic myelogenous leukemia (CML), being considered the hallmark of the disease, but around 5-8% of patients diagnosed as CML lack the Ph1 chromosome-negative (Ph-) CML has been discussed extensively in the literature because of its heterogeneity. However, it is now accepted that some of the Ph1-CML patients have a disease indistinguishable from Ph1-positive (Ph+) CML. It was investigated whether Ph- CML with clinical and morphological features indicating true CML would always have bcr rearrangements, as the relocation of c-abl from 9q34 into the breakpoint cluster region on 22q11 is considered a crucial event in the pathogenesis of CML. From molecular studies, it seemed that Ph- CML with features of true CML always have the bcr rearrangement, while Ph- patients, lacking such rearrangement, have atypical forms of CML. Here we describe 8 Ph- CML and myeloproliferative syndrome (MPS) patients of whom 6 were by all respects true CML cases. Nevertheless, bcr rearrangement and expression of the classic bcr/abl chimeric mRNA was found in only 1 of the 6 patients. More advanced molecular techniques will be needed to understand which molecular mechanisms underlie Ph-, bcr- CML, resulting in phenotypes sometimes indistinguishable from Ph+, bcr+ CML.
费城（Ph1）染色体见于大多数慢性粒细胞白血病（CML）患者，被视为该疾病的标志，但约5%-8%被诊断为CML的患者缺乏Ph1染色体。由于其异质性，Ph阴性（Ph-）CML在文献中已被广泛讨论。然而，现在人们公认，一些Ph- CML患者所患疾病与Ph阳性（Ph+）CML难以区分。研究了具有提示真性CML的临床和形态学特征的Ph- CML是否总是存在bcr重排，因为c-abl从9q34易位至22q11上的断裂点簇区域被认为是CML发病机制中的关键事件。从分子研究来看，具有真性CML特征的Ph- CML似乎总是存在bcr重排，而缺乏这种重排的Ph-患者患有非典型形式的CML。在此，我们描述了8例Ph- CML和骨髓增殖性综合征（MPS）患者，其中6例在各方面均为真性CML病例。然而，在这6例患者中仅1例发现了bcr重排和经典bcr/abl嵌合mRNA的表达。需要更先进的分子技术来了解导致Ph-、bcr- CML的分子机制，其有时会产生与Ph+、bcr+ CML难以区分的表型。
