Uckun F M, Fauci A S, Heerema N A, Song C W, Mehta S R, Gajl-Peczalska K, Chandan M, Ambrus J L
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis.
Blood. 1987 Oct;70(4):1020-34.
The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS-sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.
本研究的目的是分析B细胞生长因子（BCGF）受体的表达，并阐明经生化纯化的天然BCGF在人B淋巴细胞分化的B细胞前体阶段的生物学效应。首先研究了放射性碘化的高分子量BCGF（125I-HMW-BCGF）和低分子量BCGF（125I-LMW-BCGF）与B细胞前体急性淋巴细胞白血病（ALL）患者新鲜骨髓原始细胞的特异性结合。每个原始细胞结合的放射性碘化BCGF分子估计数量，对于HMW-BCGF，范围从检测不到到24.3×10³，对于LMW-BCGF，则从11.5×10³到457.8×10³。在³H-TdR掺入试验中，75%的病例对LMW-BCGF有显著反应，中位刺激指数为9.3。相比之下，只有33%的病例对HMW-BCGF有显著反应，中位刺激指数为2.4。随后，进行B细胞前体集落试验，以评估和比较BCGF对白血病B淋巴细胞祖细胞的生物学效应。在研究的28例病例中，57%对HMW-BCGF和LMW-BCGF均有反应，21%仅对LMW-BCGF有反应，其余病例对两种生长因子均无增殖反应。经荧光激活细胞分选术（FACS）分选的白血病B细胞前体的几乎纯群体的反应模式与未分选的白血病B细胞前体的增殖反应基本相同。在对两种因子均有反应的病例中，80%观察到HMW-BCGF和LMW-BCGF之间的协同效应。BCGF刺激培养物中细胞结合的放射性碘化BCGF分子数量、刺激指数以及B细胞前体集落数量显示出明显的患者间差异。涉及12p11-13的结构染色体异常（SCA）患者或费城染色体患者在白血病祖细胞水平上对HMW-BCGF的反应比其他患者更大（P = 0.02）。SCA患者对LMW-BCGF的反应显著大于无SCA患者（P = 0.04）。白血病祖细胞对HMW-BCGF或LMW-BCGF的反应与性别、年龄、疾病状态、FAB形态、诊断时白细胞计数或免疫表型无关。据我们所知，本研究是对B细胞前体ALL中BCGF受体表达和BCGF效应的首次详细分析。所呈现的数据为B细胞前体ALL中HMW-BCGF和LMW-BCGF功能性受体的表达提供了直接证据。
