The Saint Luke's Cancer Institute, 4321 Washington, Suite 4000 Kansas City, Missouri 64111, USA.
J Hematol Oncol. 2009 Dec 29;2:51. doi: 10.1186/1756-8722-2-51.
We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.
我们描述了一种严重联合免疫缺陷（SCID）小鼠模型，该模型允许原发性人急性白血病原始细胞在皮下生长成可测量的皮下结节，随后可能发展为播散性疾病。利用 SCID 小鼠模型，我们在未经预处理的情况下，检查了来自 133 例急性白血病患者（67 例急性淋巴细胞白血病（ALL）和 66 例急性髓系白血病（AML））的白血病原始细胞在动物体内的生长潜力。这些原始细胞显示出三种不同的生长模式：“侵袭性”、“惰性”或“无肿瘤生长”。在 133 例白血病中，45 例（33.8%）表现出侵袭性生长模式，14 例（10.5%）表现出惰性生长模式，74 例（55.6%）在 SCID 小鼠中未生长。复发和/或难治性疾病的白血病的生长概率几乎是初诊疾病患者的 3 倍。连续观察发现，来自同一患者的白血病原始细胞，如果在初始表现和/或早期复发时未引发肿瘤生长，可能会在疾病的后期植入和生长，这表明白血病细胞的植入和增殖能力是随着白血病进展的过程逐渐获得的。我们在体外建立了 9 个自主生长的白血病细胞系。这些细胞系显示出侵袭性增殖模式，这表明人类白血病细胞在体外自主增殖的能力与在 SCID 小鼠中侵袭性生长的潜力之间可能存在相关性。此外，我们还证明，在 SCID 小鼠中白血病原始细胞表现出侵袭性生长和播散模式的患者，其 ALL 和 AML 的临床结局较差。白血病原始细胞生长缓慢或白血病细胞未能诱导生长的患者，DFS 明显更长，临床过程更为有利。
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