Ligler F S, Brodsky I, Schlam M L, Fuscaldo K E
Leuk Res. 1985;9(9):1093-8. doi: 10.1016/0145-2126(85)90097-9.
Thirty-nine patients with Philadelphia chromosome-positive (Ph1) chronic myelocytic leukemia (CML) were monitored using cytofluorometry and cytogenetics. During chronic phase, abnormal populations could be detected using commercially available monoclonal antibodies. Most of these abnormal populations had either an HLA.DR+ or an OKM1+ HLA.DR- phenotype. Thirteen patients progressed to acute phase disease. Five patients with HLA-DR+ abnormal cells during chronic phase showed no clonal evolution detectable using standard cytogenetic techniques and underwent lymphoid transformation. Seven patients with OKM1+-HLA.DR- abnormal cells exhibited chromosomal abnormalities in addition to the Ph1 and progressed to a myeloblastic acute phase. One patient with HLA.DR+ OKM1+ 63D3+ abnormal cells in chronic phase showed clonal evolution and progressed to a myelomonocytic acute phase. These results suggest that cell surface markers on chronic phase cells can be used in conjunction with cytogenetic monitoring to predict the phenotype of cells involved in the acute transformation of CML. B cells (6, 13), but not T cells (18), bearing the Ph1 have been isolated from chronic phase CML patients. Thus cells other than those of myeloid lineage may be involved. Periodic cytogenetic monitoring has been shown to detect clonal evolution (i.e. genetic changes in addition to the PH1) in as many as 75% of patients prior to the acute phase (14, 37). However, neither cytogenetic changes nor morphologic analysis appear to predict the lymphoblastic type of transformation (14). Since fluorescence analysis of cell surface markers has shown reduced numbers of normal cells (28), the identity of the 'abnormal' cells was probed with antibodies recognizing a variety of markers on immature and mature lymphoid and myeloid cells. Not only were significant numbers of abnormal cells detected in the peripheral blood of chronic phase patients, but the phenotype of the abnormal population, in combination with cytogenetic analyses, predicted the type of blasts involved in acute phase disease.
采用细胞荧光测定法和细胞遗传学方法对39例费城染色体阳性（Ph1）的慢性粒细胞白血病（CML）患者进行了监测。在慢性期，使用市售单克隆抗体可检测到异常细胞群。这些异常细胞群大多具有HLA.DR + 或OKM1 + HLA.DR - 表型。13例患者进展为急性期疾病。5例在慢性期有HLA - DR + 异常细胞的患者，使用标准细胞遗传学技术未检测到克隆进化，并发生了淋巴细胞转化。7例具有OKM1 + -HLA.DR - 异常细胞的患者除Ph1外还表现出染色体异常，并进展为成髓细胞急性期。1例在慢性期具有HLA.DR + OKM1 + 63D3 + 异常细胞的患者出现克隆进化，并进展为粒单核细胞急性期。这些结果表明，慢性期细胞的细胞表面标志物可与细胞遗传学监测结合使用，以预测CML急性转化中所涉及细胞的表型。已从慢性期CML患者中分离出携带Ph1的B细胞（6,13），但未分离出T细胞（18）。因此，可能涉及髓系谱系以外的细胞。已证明定期细胞遗传学监测可在急性期之前检测到多达75%的患者中的克隆进化（即除Ph1外的基因变化）（14,37）。然而，细胞遗传学变化和形态学分析似乎均无法预测淋巴细胞转化类型（14）。由于细胞表面标志物的荧光分析显示正常细胞数量减少（28），因此用识别未成熟和成熟淋巴细胞及髓细胞上多种标志物的抗体对“异常”细胞的身份进行了探究。不仅在慢性期患者的外周血中检测到大量异常细胞，而且异常细胞群的表型与细胞遗传学分析相结合，可预测急性期疾病中所涉及的原始细胞类型。
