Hu Z B, Ma W, Zaborski M, MacLeod R, Quentmeier H, Drexler H G
DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Leukemia. 1996 Jun;10(6):1025-40.
Human permanent leukemia cell lines represent powerful research tools in a multitude of investigations. The two new continuous leukemia cell lines MUTZ-2 and MUTZ-3 were derived from the peripheral blood of patients with acute myeloid leukemia (AML) FAB M2 and AML FAB M4. MUTZ-2 and MUTZ-3 cells have morphological and immunophenotypical features of myeloid and monocytic cells, respectively. While MUTZ-2 is negative, MUTZ-3 cells express the monocytic surface marker CD14, albeit weakly. The monocytic nature of MUTZ-3 cells is underlined by the expression of the monocyte-specific esterase (MSE), myeloperoxidase (MPO) and tartrateresistant acid phosphatase (TRAP) enzymes; MUTZ-2 is negative for MSE and TRAP, but expresses MPO. For sustained cell growth, both cell lines require constitutively the addition of cytokines to the culture medium and retain an absolute dependence on conditioned medium or recombinant growth factors for proliferation and survival. Incubation with single recombinant cytokines from a broad spectrum of growth factors established that the strongest proliferation response of MUTZ-2 cells was elicited by FLT-3 ligand, granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), interferon-gamma (IFN-gamma) and stem cell factor (SCF), whereas granulocyte-macrophage CSF (GM-CSF), M-CSF, interleukin-3 (IL-3) and SCF were the most effective growth factors in inducing proliferation of MUTZ-3. Both cell lines were proliferatively responsive to several further cytokines, however, to a lesser extent. Exposure to phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or the physiological all-trans retinoic acid (ATRA) had growth-inhibitory and differentiation-inducing effects on both cell lines. Using a clonogenic cell recovery assay, both cell lines were found to be sensitive to the chemotherapeutic drugs cytosine arabinoside (Ara-C) and daunorubicin (DNR), MUTZ-2 cells being more sensitive to both Ara-C and DNR treatment than MUTZ-3 cells. Chromosomal trisomies 8 and 10 were found in MUTZ-2 cells without any additional structural abnormalities. MUTZ-3 carries the rare, but recurrent AML-associated translocation (12;22)(p13;q11-q12) reflecting the karyotype of the original tumor. The main characteristics of these cell lines remained the same during about 1 year of continuous culture as well as after freezing and thawing. In summary, we established and characterized two new leukemia cell lines with myeloid or monocytic features which are growth factor-responsive, one of them carrying a unique chromosomal translocation. These cells will be of particular value for investigating the complex cytokine network and molecular events caused by chromosomal aberrations.
人类永久性白血病细胞系是众多研究中强大的研究工具。两种新的连续白血病细胞系MUTZ - 2和MUTZ - 3源自急性髓系白血病（AML）FAB M2和AML FAB M4患者的外周血。MUTZ - 2和MUTZ - 3细胞分别具有髓系和单核细胞的形态学和免疫表型特征。MUTZ - 2呈阴性，而MUTZ - 3细胞表达单核细胞表面标志物CD14，尽管表达较弱。MUTZ - 3细胞的单核细胞性质通过单核细胞特异性酯酶（MSE）、髓过氧化物酶（MPO）和抗酒石酸酸性磷酸酶（TRAP）的表达得以体现；MUTZ - 2对MSE和TRAP呈阴性，但表达MPO。为实现细胞的持续生长，两种细胞系在培养基中持续需要添加细胞因子，并且在增殖和存活方面对条件培养基或重组生长因子保持绝对依赖。用一系列广泛的生长因子中的单一重组细胞因子进行孵育发现，FLT - 3配体、粒细胞集落刺激因子（G - CSF）、巨噬细胞集落刺激因子（M - CSF）、干扰素 - γ（IFN - γ）和干细胞因子（SCF）对MUTZ - 2细胞引发最强的增殖反应，而粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）、M - CSF、白细胞介素 - 3（IL - 3）和SCF是诱导MUTZ - 3增殖最有效的生长因子。然而，两种细胞系对其他几种细胞因子也有增殖反应，只是程度较小。暴露于佛波酯12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）或生理性全反式维甲酸（ATRA）对两种细胞系均有生长抑制和诱导分化的作用。使用克隆形成细胞恢复试验发现，两种细胞系对化疗药物阿糖胞苷（Ara - C）和柔红霉素（DNR）均敏感，MUTZ - 2细胞对Ara - C和DNR治疗均比MUTZ - 3细胞更敏感。在MUTZ - 2细胞中发现了8号和10号染色体三体，没有任何其他结构异常。MUTZ - 3携带罕见但反复出现的与AML相关的易位（12；22）（p13；q11 - q12），反映了原始肿瘤的核型。在连续培养约1年以及冻融后，这些细胞系的主要特征保持不变。总之，我们建立并鉴定了两种具有髓系或单核细胞特征的新白血病细胞系，它们对生长因子有反应，其中之一携带独特的染色体易位。这些细胞对于研究复杂的细胞因子网络以及由染色体畸变引起的分子事件将具有特殊价值。
