Carow C E, Levenstein M, Kaufmann S H, Chen J, Amin S, Rockwell P, Witte L, Borowitz M J, Civin C I, Small D
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287-5001, USA.
Blood. 1996 Feb 1;87(3):1089-96.
Normal expression of the hematopoietic growth factor receptor FLT3 (STK-1@Flk2) is limited to CD34+ stem/progenitor cells. We have evaluated the expression of FLT3 by RNase protection assay and Western blotting in 161 primary bone marrow (BM) samples from patients with leukemia. FLT3 RNA was found to be expressed at a higher level than in normal BM controls in 33 of 33 B-lineage acute leukemias, 11 of 12 acute myeloid leukemias (AMLs), and 3 of 11 T-cell acute leukemias (T-ALLs). Expression of FLT3 RNA was also observed in some cases of blast crisis CML. The FLT3 signal resulted from expression on the leukemic blasts, and was not caused by increased FLT3 expression on normal CD34+ stem/progenitor cells in the leukemic samples. To determine if FLT3 protein was also overexpressed, proteins were extracted from leukemic BM samples and screened by Western blotting with anti-FLT3 antisera. FLT3 protein was not detected in normal BM controls, but was found in 14 of 14 B-lineage ALLs, 36 of 41 AMLs, and 1 of 4 T-ALLs. Stimulation of patient samples with FLT3 ligand resulted in autophosphorylation of the FLT3 receptor, suggesting the receptor is functional in these cells. These data show that FLT3 RNA and protein are aberrantly expressed by AML and ALL cells in that CD34 expression and FLT3 expression are no longer synchronous, and suggest the possibility that overexpression of FLT3 could play a role in the survival and/or proliferation of malignant clones in acute myeloid and lymphoid leukemias.
造血生长因子受体FLT3（STK-1@Flk2）的正常表达仅限于CD34+干/祖细胞。我们通过核糖核酸酶保护分析和蛋白质印迹法评估了161例白血病患者原发性骨髓（BM）样本中FLT3的表达。在33例B系急性白血病、12例急性髓性白血病（AML）中的11例以及11例T细胞急性白血病（T-ALL）中的3例中，发现FLT3 RNA的表达水平高于正常BM对照。在一些慢性粒细胞白血病急变期病例中也观察到FLT3 RNA的表达。FLT3信号源自白血病原始细胞上的表达，而非白血病样本中正常CD34+干/祖细胞上FLT3表达增加所致。为确定FLT3蛋白是否也过表达，从白血病BM样本中提取蛋白质，并用抗FLT3抗血清通过蛋白质印迹法进行筛查。在正常BM对照中未检测到FLT3蛋白，但在14例B系ALL中的14例、41例AML中的36例以及4例T-ALL中的1例中发现了该蛋白。用FLT3配体刺激患者样本导致FLT3受体自磷酸化，表明该受体在这些细胞中具有功能。这些数据表明，AML和ALL细胞异常表达FLT3 RNA和蛋白，即CD34表达和FLT3表达不再同步，并提示FLT3过表达可能在急性髓性和淋巴细胞白血病恶性克隆的存活和/或增殖中起作用。
