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建立并鉴定人急性髓单核细胞白血病细胞系 JIH-3。

Establishment and characterization of a new human acute myelomonocytic leukemia cell line JIH-3.

机构信息

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Suzhou, PR China.

出版信息

Leuk Res. 2012 Jul;36(7):889-94. doi: 10.1016/j.leukres.2012.01.012. Epub 2012 Feb 14.

Abstract

Here, a new acute myelomonocytic leukemia (AMML) cell line, JIH-3, is reported, and its biological characteristics are described. JIH-3 cells were maintained without any cytokines for 27 months. The JIH-3 cell line showed typical myelomonocytic morphological features. Additionally, it mainly expressed myeloid and monocytic markers (CD13, CD14, CD11b, CD15 and CD33), although it also expressed other antigens such as the markers of T and B lymphocytic lineage as well as stem cell, progenitor cell, and natural killer cell-related antigens (CD4, CD5, CD7, CD10, CD22, CD34, CD38, HLADR, CD16/CD56 and CD56); the expression of these markers, suggested that this cell line was in the early stage of myelomonocytic differentiation. Cytogenetic analysis initially showed a karyotype of 46, XY, del(7) (p1?3p2?2). During the passage period, the cells with this karyotype gradually decreased and were replaced by cells with a 45,XY,dic(4;7)(p11;p11),del(15)(q2?2) karyotype. Chromosome painting showed a deletion in the short arm of chromosome 7 for del(7)(p1?3p2?2) and der(4;7)(p11;p11). The latter had larger deleted segment than the former. Fluorescence in situ hybridization (FISH) revealed the dicentric nature of der(4;7), and Multiplex FISH (M-FISH) confirmed that der(4;7) was an unbalanced translocation. A deletion involving the 7p region on dic(4;7)(p11;p11) harbors many genes, including CDC2L5, C7ORF11, C7ORF10 and INHBA. Haploinsufficiency of the genes on 4p, 7p and 15q caused by deletions of 4p, 7p and 15q2?2 that resulted from dic(4;7)(p11;p11) and del(15)(q2?2) may play important roles in leukemogenesis and in the establishment of the JIH-3 cell line. JIH-3 cells did not express multidrug resistance (MDR)-related genes and apoptosis-related genes such as MDR1, multidrug resistance-related protein, lung resistance protein, BCL-2, Bax, GS-π or Fax, only P21 expression was detected, which probably leads the MDR indirectly through inhibition of the activities of cyclin-dependent kinase (CDK). JIH-3 cells had tumorigenic capacity in nude mice. In conclusion, JIH-3 is a new acute myelomonocytic leukemia cell line. It is from a well-characterized background and provides a new useful tool for the study of leukemia patients with a 7p deletion.

摘要

这里报告了一种新的急性髓单核细胞白血病(AMML)细胞系 JIH-3,并描述了其生物学特征。JIH-3 细胞在没有任何细胞因子的情况下维持了 27 个月。JIH-3 细胞系表现出典型的髓单核细胞形态特征。此外,它主要表达髓系和单核细胞标志物(CD13、CD14、CD11b、CD15 和 CD33),尽管它还表达其他抗原,如 T 和 B 淋巴细胞谱系以及干细胞、祖细胞和自然杀伤细胞相关抗原(CD4、CD5、CD7、CD10、CD22、CD34、CD38、HLADR、CD16/CD56 和 CD56);这些标志物的表达表明该细胞系处于髓单核细胞分化的早期阶段。细胞遗传学分析最初显示核型为 46,XY,del(7)(p1?3p2?2)。在传代过程中,具有这种核型的细胞逐渐减少,并被具有 45,XY,dic(4;7)(p11;p11),del(15)(q2?2)核型的细胞取代。染色体涂染显示 7 号染色体短臂缺失 del(7)(p1?3p2?2)和 der(4;7)(p11;p11)。后者缺失的片段比前者大。荧光原位杂交(FISH)显示 der(4;7)的双中心性质,多重荧光原位杂交(M-FISH)证实 der(4;7)是不平衡易位。dic(4;7)(p11;p11)上涉及 7p 区域的缺失包含许多基因,包括 CDC2L5、C7ORF11、C7ORF10 和 INHBA。4p、7p 和 15q2?2 缺失导致的 4p、7p 和 15q 缺失引起的基因单倍不足,可能在白血病发生和 JIH-3 细胞系建立中发挥重要作用。JIH-3 细胞不表达多药耐药(MDR)相关基因和凋亡相关基因,如 MDR1、多药耐药相关蛋白、肺耐药蛋白、BCL-2、Bax、GS-π 或 Fax,仅检测到 P21 表达,这可能通过抑制细胞周期蛋白依赖性激酶(CDK)的活性间接导致 MDR。JIH-3 细胞在裸鼠中有致瘤能力。总之,JIH-3 是一种新的急性髓单核细胞白血病细胞系。它具有明确的背景,为研究具有 7p 缺失的白血病患者提供了一种新的有用工具。

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