O'Connor R, Cesano A, Lange B, Finan J, Nowell P C, Clark S C, Raimondi S C, Rovera G, Santoli D
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Blood. 1991 Apr 1;77(7):1534-45.
Cells from 10 cases of childhood acute T-lymphoblastic leukemia (T-ALL) were cultured in the presence of recombinant human interleukins (rhIL) or colony-stimulating factors (CSF) to analyze their growth factor requirements and differentiative potential. Although cells from most leukemic samples displayed a short-term proliferative response to several hematopoietic growth factors, only the ones featuring chromosomal translocations could be established as permanent cell lines. Two cell lines could be initiated only in the presence of IL-3 (TALL-103 and TALL-106), one in granulocyte-macrophage CSF (GM-CSF) (TALL-101), and one in IL-2 (TALL-104); only one cell line (TALL-105) was originated in the absence of growth factors. The TALL-101 and TALL-103 cell lines, derived from very immature T-ALL cases, underwent growth factor-dependent phenotypic conversion (lymphoid to myeloid). However, the T-cell receptor rearrangement and karyotype of the original leukemic clones were retained. In contrast, the TALL-104, -105, and -106 cell lines which originated from more mature T-ALL cases, maintained a T-lymphoblastic phenotype regardless of the growth factors in which they were expanded. These data demonstrate in vitro the aggressive nature of T-ALL cases bearing chromosomal abnormalities, and indicate that the lineage commitment of the malignant clone depends on its stage of maturation in T-cell ontogeny.
培养来自10例儿童急性T淋巴细胞白血病(T-ALL)的细胞,同时加入重组人白细胞介素(rhIL)或集落刺激因子(CSF),以分析其对生长因子的需求和分化潜能。尽管大多数白血病样本的细胞对几种造血生长因子表现出短期增殖反应,但只有具有染色体易位的细胞才能建立为永久细胞系。仅在IL-3存在的情况下可启动两个细胞系(TALL-103和TALL-106),在粒细胞-巨噬细胞集落刺激因子(GM-CSF)存在的情况下启动一个细胞系(TALL-101),在IL-2存在的情况下启动一个细胞系(TALL-104);仅一个细胞系(TALL-105)在无生长因子的情况下产生。源自非常不成熟的T-ALL病例的TALL-101和TALL-103细胞系经历了生长因子依赖性表型转化(从淋巴细胞到髓细胞)。然而,原始白血病克隆的T细胞受体重排和核型得以保留。相反,源自更成熟T-ALL病例的TALL-104、-105和-106细胞系,无论在何种生长因子中扩增,均维持T淋巴细胞母细胞表型。这些数据在体外证明了具有染色体异常的T-ALL病例的侵袭性,并表明恶性克隆的谱系定向取决于其在T细胞个体发生中的成熟阶段。