Hittelman W N, Agbor P, Petkovic I, Andersson B, Kantarjian H, Walters R, Koller C, Beran M
Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Blood. 1988 Dec;72(6):1950-60.
The purpose of this study was to determine the feasibility of using the technique of premature chromosome condensation to detect the in vivo maturation of abnormal elements in patients with chronic myelogenous leukemia (CML), myelodysplastic syndrome, and acute leukemia. Patients were chosen for study if there were a clinical suggestion of in vivo maturation and a leukemic clone exhibiting a distinguishable karyotypic abnormality. Mature peripheral blood granulocytes were enriched by two-step Ficoll-Hypaque gradient sedimentation and fused with mitotic Chinese hamster ovary cells to induce the formation of prematurely condensed chromosomes (PCC). These PCC were then analyzed for chromosome number per cell (in the case of patients with a numerical abnormality) or by G-banding (in the case of specific translocations). Of 13 patients chosen for study, 12 showed karyotypic evidence for maturation of the abnormal elements in vivo. Maturation was observed in a number of clinical situations including before treatment in benign CML and myelodysplasia, after low-dose and high-dose chemotherapy in myelodysplasia and acute myelogenous leukemia (AML), and in remission. These results suggest that the technique of premature chromosome condensation can be a powerful tool in better understanding the biology of disease and mode of response to therapy in vivo in patients with leukemia and preleukemic syndromes, especially during treatment with agents thought to induce maturation of the leukemic elements.
本研究的目的是确定使用早熟染色体凝集技术检测慢性粒细胞白血病（CML）、骨髓增生异常综合征和急性白血病患者体内异常细胞成分成熟情况的可行性。如果患者有体内成熟的临床提示且白血病克隆表现出可区分的核型异常，则入选本研究。通过两步法Ficoll-泛影葡胺梯度沉降富集成熟外周血粒细胞，并使其与有丝分裂期的中国仓鼠卵巢细胞融合，以诱导早熟染色体（PCC）的形成。然后对这些PCC进行分析，计算每个细胞的染色体数目（对于有数目异常的患者）或进行G显带分析（对于特定易位的情况）。在入选研究的13例患者中，12例显示出体内异常细胞成分成熟的核型证据。在多种临床情况下观察到了成熟现象，包括良性CML和骨髓增生异常综合征治疗前、骨髓增生异常综合征和急性髓系白血病（AML）低剂量和高剂量化疗后以及缓解期。这些结果表明，早熟染色体凝集技术可能是一种有力的工具，有助于更好地理解白血病和白血病前期综合征患者体内疾病的生物学特性及对治疗的反应模式，尤其是在用被认为可诱导白血病细胞成分成熟的药物治疗期间。
