Costello R, Lafage M, Toiron Y, Brunel V, Sainty D, Arnoulet C, Mozziconacci M J, Bouabdallah R, Gastaut J A, Maraninchi D
Haematology Department, Centre Anti-Cancéreux de Marseille, France.
Br J Haematol. 1995 Jun;90(2):346-52. doi: 10.1111/j.1365-2141.1995.tb05157.x.
The Philadelphia chromosome (Ph) is the cytogenetic hallmark of chronic myeloid leukaemia (CML) and is used to confirm the diagnosis of CML based on clinical and morphological criteria. We investigated 14 patients with features of CML but without detectable Ph chromosome. In seven patients, referred to as BCR+, M-bcr/abl rearrangement was detected by polymerase chain reaction (PCR). The seven remaining patients did not have M-bcr/abl rearrangement and are described as BCR-. BCR- patients were younger, had lower white blood cell counts (WBC) and lower basophilia. Four BCR- and four BCR+ patients underwent blastic transformation (BT). Response to therapy was fairly similar in both populations. According to French-American-British (FAB) Cooperative Leukaemia Group guidelines, all BCR- patients were classified as having classic form CML or 'chronic granulocytic leukaemia' (CGL) when based only on morphological data. This study further confirms the existence of true CML cases without Ph chromosome or M-bcr/abl rearrangement and shows that this entity differs only slightly from classic form Ph+ CML. The Ph-BCR- subgroup raises two problems. First, the differential diagnosis with atypical CML or CMML, based on morphological data, and secondly, the therapeutic follow-up in the absence of a specific marker. In contrast, the residual disease of Ph-BCR- patients can be monitored by PCR. More advanced molecular and biochemical techniques will be required to understand which molecular mechanisms underlie Ph-BCR- CML, resulting in phenotypes sometimes indistinguishable from Ph+ CML.
费城染色体（Ph）是慢性髓性白血病（CML）的细胞遗传学标志，用于根据临床和形态学标准确诊CML。我们研究了14例具有CML特征但未检测到Ph染色体的患者。在7例患者中，通过聚合酶链反应（PCR）检测到M-bcr/abl重排，这些患者被称为BCR+。其余7例患者没有M-bcr/abl重排，被描述为BCR-。BCR-患者年龄较小，白细胞计数（WBC）较低，嗜碱性粒细胞较少。4例BCR-患者和4例BCR+患者发生了急变（BT）。两个群体对治疗的反应相当相似。根据法美英（FAB）白血病协作组的指南，仅根据形态学数据，所有BCR-患者都被归类为具有经典型CML或“慢性粒细胞白血病”（CGL）。本研究进一步证实了存在无Ph染色体或M-bcr/abl重排的真正CML病例，并表明该实体与经典型Ph+CML仅略有不同。Ph-BCR-亚组引发了两个问题。第一，基于形态学数据与非典型CML或CMML的鉴别诊断；第二，在缺乏特异性标志物的情况下的治疗随访。相比之下，Ph-BCR-患者的残留疾病可以通过PCR进行监测。需要更先进的分子和生化技术来了解Ph-BCR-CML的分子机制，这些机制有时会导致其表型与Ph+CML难以区分。
