Fuscaldo K E, Brodsky I, Crilley P, Ligler F S
Cancer Genet Cytogenet. 1987 May;26(1):25-37. doi: 10.1016/0165-4608(87)90130-0.
Chronic myelocytic leukemia (CML) is a model system for the study of many aspects of malignant disease. One aspect that correlates with decreasing therapeutic response is tumor progression. This progression is often accompanied by clonal evolution. In those cases where aggressive therapy does not prevent this evolution, the clinical response to therapy usually proves to be poor and of short duration. Investigators are concentrating their efforts in three primary, but not mutually exclusive, areas with respect to the clinical management of CML. These include: an attempt to distinguish patients at risk for early transformation from those who will have a prolonged chronic phase; the cryopreservation of autologous bone marrow or buffy coat early in chronic phase for subsequent use in the accelerated phase and; endeavors to identify early markers for disease progression allowing intervention before an irreversible blast crisis occurs. This report deals with two types of potential prognostic markers of transformation: chromosomal and cell surface characteristics. The appearance of nonrandom abnormal chromosomal patterns has been correlated with myeloblastic transformation by many investigators. However, there has always been a subset of CML patients who do not undergo clonal evolution. Additionally, the type(s) of transformation in CML may vary depending on the cell lineages involved. Unlike myeloblastic transformants, many of our patients who do not exhibit clonal evolution as a concomitance of disease progression develop a lymphoblastic transformation. Cytofluorometric analysis can distinguish small populations of abnormal cells with lymphoblastic characteristics (HLA DR+). Initial data suggests that patients expressing the HLA DR+ in their "normal" peripheral blood cells are at risk of undergoing lymphoblastic transformation. The combined use of clinical, cytogenetic, and cytofluorometric data to predict an impending transformation and to discriminate between myeloblastic and lymphoblastic populations allows clinicians to manage their patients more effectively.
慢性粒细胞白血病（CML）是研究恶性疾病诸多方面的一个模型系统。与治疗反应降低相关的一个方面是肿瘤进展。这种进展通常伴随着克隆进化。在积极治疗无法阻止这种进化的情况下，临床治疗反应通常较差且持续时间短。关于CML的临床管理，研究人员正将精力集中在三个主要但并非相互排斥的领域。这些领域包括：试图区分有早期转化风险的患者和将有较长慢性期的患者；在慢性期早期冷冻保存自体骨髓或血沉棕黄层，以供加速期后续使用；努力识别疾病进展的早期标志物，以便在不可逆转的原始细胞危象发生之前进行干预。本报告涉及两种潜在的转化预后标志物：染色体和细胞表面特征。许多研究人员已将非随机异常染色体模式的出现与髓母细胞转化相关联。然而，总有一部分CML患者不会经历克隆进化。此外，CML的转化类型可能因涉及的细胞谱系而异。与髓母细胞转化体不同，我们的许多未表现出作为疾病进展伴随情况的克隆进化的患者会发生淋巴细胞转化。细胞荧光分析可以区分具有淋巴细胞特征（HLA DR+）的少量异常细胞。初步数据表明，在其“正常”外周血细胞中表达HLA DR+的患者有发生淋巴细胞转化的风险。综合使用临床、细胞遗传学和细胞荧光分析数据来预测即将发生的转化，并区分髓母细胞和淋巴细胞群体，可使临床医生更有效地管理患者。
