Feuring-Buske M, Haase D, Buske C, Hiddemann W, Wörmann B
Department of Internal Medicine, Georg-August-University, Göttingen, Germany.
Leukemia. 1999 Mar;13(3):386-92. doi: 10.1038/sj.leu.2401300.
Acute myeloid leukemia arises from the clonal expansion of a malignant transformed progenitor cell. Despite intensive chemotherapy, final disease eradication is achieved by a small proportion of cases only and 50-70% of adults with AML will ultimately relapse and die from their disease. Hence residual disease below the level of morphological detectability must be assumed in clinical and morphological complete remission. CD34+/CD38- and CD34+/CD38+ subpopulations of seven patients in morphological complete remission were isolated by FACS (purity >98%) and were analyzed by conventional cytogenetics or FISH for chromosomal aberrations. In five of seven patients, clonal chromosomal abnormalities were detected in the CD34+/CD38+ subpopulation and in one patient with AML M2 (add (2)(q37)) in the most immature CD34+/CD38- stem cell compartment. One patient with AML M4Eo (inv(16),+8), showed a normal karyotype by conventional cytogenetic analysis, whereas four of 15 metaphases of the sorted CD34+/CD38+ subpopulation revealed the inversion 16. These observations underline that leukemic cells can survive intensive chemotherapy in the niche of the stem cell compartment. In some patients the sensitivity for the detection of persistent leukemic cells seems to be higher in FACS-sorted subpopulations than conventional cytogenetic analysis of the unseparated bone marrow. Immunophenotyping revealed minimal residual disease in four of the patients. Functional analysis has to be performed to investigate the leukemogenic potential of these residual cells.
急性髓系白血病源于恶性转化祖细胞的克隆性扩增。尽管进行了强化化疗，但只有一小部分病例能最终根除疾病，50 - 70%的成年急性髓系白血病患者最终会复发并死于该疾病。因此，在临床和形态学完全缓解时，必须假定存在形态学可检测水平以下的残留疾病。通过荧光激活细胞分选术（FACS）分离出形态学完全缓解的7例患者的CD34 + / CD38 - 和CD34 + / CD38 + 亚群（纯度> 98%），并通过常规细胞遗传学或荧光原位杂交（FISH）分析染色体畸变。在7例患者中的5例中，在CD34 + / CD38 + 亚群中检测到克隆性染色体异常，在1例急性髓系白血病M2型（add(2)(q37)）患者的最不成熟的CD34 + / CD38 - 干细胞区室中也检测到异常。1例急性髓系白血病M4Eo型（inv(16), +8）患者，常规细胞遗传学分析显示核型正常，而分选的CD34 + / CD38 + 亚群的15个中期细胞中有4个显示16号染色体倒位。这些观察结果强调白血病细胞能够在强化化疗后于干细胞区室的微环境中存活。在一些患者中，荧光激活细胞分选术分选的亚群中检测持续存在的白血病细胞的敏感性似乎高于未分离骨髓的常规细胞遗传学分析。免疫表型分析在4例患者中检测到微小残留病。必须进行功能分析以研究这些残留细胞的白血病发生潜能。
