Haase D, Feuring-Buske M, Könemann S, Fonatsch C, Troff C, Verbeek W, Pekrun A, Hiddemann W, Wörmann B
Department of Hematology and Oncology, University of Göttingen, Germany.
Blood. 1995 Oct 15;86(8):2906-12.
Acute myeloid leukemia (AML) is a heterogenous disease according to morphology, immunophenotype, and genetics. The retained capacity of differentiation is the basis for the phenotypic classification of the bulk population of leukemic blasts and the identification of distinct subpopulations. Within the hierarchy of hematopoietic development and differentiation it is still unknown at which stage the malignant transformation occurs. It was our aim to analyze the potential involvement of cells with the immunophenotype of pluripotent stem cells in the leukemic process by the use of cytogenetic and cell sorting techniques. Cytogenetic analyses of bone marrow aspirates were performed in 13 patients with AML (11 de novo and 2 secondary) and showed karyotype abnormalities in 10 cases [2q+, +4, 6p, t(6:9), 7, +8 in 1 patient each and inv(16) in 4 patients each]. Aliquots of the samples were fractionated by fluorescence-activated cell sorting of CD34+ cells. Two subpopulations, CD34+/CD38- (early hematopoietic stem cells) and CD34+/CD38+ (more mature progenitor cells), were screened for karyotype aberations as a marker for leukemic cells. Clonal abnormalities and evaluable metaphases were found in 8 highly purified CD34+/CD38- populations and in 9 of the CD34+/CD38- specimens, respectively. In the majority of cases (CD34+/CD38-, 6 of 8 informative samples; CD34+/CD38+, 5 of 9 informative samples), the highly purified CD34+ specimens also contained cytogenetically normal cells. Secondary, progression-associated chromosomal changes (+8, 12) were identified in the CD34+/CD38- cells of 2 patients. We conclude that clonal karyotypic abnormalities are frequently found in the stem cell-like (CD34+/CD38-) and more mature (CD34+/CD38+) populations of patients with AML, irrespective of the phenotype of the bulk population of leukemic blasts and of the primary or secondary character of the leukemia. Our data suggest that, in AML, malignant transformation as well as disease progression may occur at the level of CD34+/CD38- cells with multilineage potential.
急性髓系白血病（AML）在形态学、免疫表型和遗传学方面是一种异质性疾病。白血病原始细胞大量群体的表型分类以及不同亚群的识别，其基础是保留的分化能力。在造血发育和分化的层级结构中，恶性转化发生在哪个阶段仍然未知。我们的目的是通过细胞遗传学和细胞分选技术，分析具有多能干细胞免疫表型的细胞在白血病过程中的潜在参与情况。对13例AML患者（11例初发和2例继发）的骨髓穿刺液进行了细胞遗传学分析，10例显示核型异常[1例患者分别为2q +、+4、6p、t(6;9)、7、+8，4例患者为inv(16)]。通过对CD34 +细胞进行荧光激活细胞分选，将样本等分。筛选了两个亚群，CD34 + /CD38 -（早期造血干细胞）和CD34 + /CD38 +（更成熟的祖细胞），以检测核型畸变作为白血病细胞的标志物。分别在8个高度纯化的CD34 + /CD38 -群体和9个CD34 + /CD38 +样本中发现了克隆异常和可评估的中期分裂相。在大多数情况下（CD34 + /CD38 -，8个信息样本中的6个；CD34 + /CD38 +，9个信息样本中的5个），高度纯化的CD34 +样本也包含细胞遗传学正常的细胞。其次，在2例患者的CD34 + /CD38 -细胞中鉴定出与疾病进展相关的继发性染色体变化（+8、12）。我们得出结论，AML患者的干细胞样（CD34 + /CD38 -）和更成熟（CD34 + /CD38 +）群体中经常发现克隆核型异常，无论白血病原始细胞大量群体的表型以及白血病的原发或继发性质如何。我们的数据表明，在AML中，具有多系潜能的CD34 + /CD38 -细胞水平可能发生恶性转化以及疾病进展。
