Rosnet O, Bühring H J, Marchetto S, Rappold I, Lavagna C, Sainty D, Arnoulet C, Chabannon C, Kanz L, Hannum C, Birnbaum D
Laboratoire d'Oncologie Moléculaire, INSERM U119, Marseille, France.
Leukemia. 1996 Feb;10(2):238-48.
FLT3/FLK2 is a receptor tyrosine kinase (RTK) which is thought to play an important role in early stages of hematopoiesis. Monoclonal antibodies (mAbs) against the extracellular domain of human FLT3 were generated to study the cell surface expression of this class III RTK on normal bone marrow cells and on leukemic blasts from patients with acute leukemias. Functional analysis of five mAbs (SF1 series) revealed that all of them can mimic to variable extents the activity of the FLT3 ligand (FL) upon receptor activation and modulation, while only one mAb weakly inhibited ligand binding. Using flow cytometry, we detected surface expression of FLT3 on cell lines of the myeloid (4/8) and B lymphoid (7/10) lineages. On normal human bone marrow cells, the expression of FLT3 is restricted, in agreement with a presumed function of this receptor at the level of the stem cells and early committed progenitors. Expression of FLT3 was found on a fraction of CD34-positive and CD34-negative cells. Three-color analysis further revealed that most of the CD34 FLT3+ cells coexpress CD117 (KIT) at a high level. Finally, FLT3 is expressed on leukemic blasts of 18/22 acute myeloid leukemias (AML) and 3/5 acute lymphoid leukemias (ALL) of the B lineage, providing a possible application in diagnosis and therapy of these diseases.
FLT3/FLK2是一种受体酪氨酸激酶（RTK），被认为在造血早期阶段发挥重要作用。我们制备了针对人FLT3胞外结构域的单克隆抗体（mAb），以研究这种III类RTK在正常骨髓细胞和急性白血病患者白血病原始细胞上的细胞表面表达。对五种单克隆抗体（SF1系列）的功能分析表明，它们在受体激活和调节时都能不同程度地模拟FLT3配体（FL）的活性，而只有一种单克隆抗体能微弱地抑制配体结合。我们使用流式细胞术检测了髓系（4/8）和B淋巴细胞系（7/10）细胞系上FLT3的表面表达。在正常人骨髓细胞上，FLT3的表达受到限制，这与该受体在干细胞和早期定向祖细胞水平上的假定功能一致。在一部分CD34阳性和CD34阴性细胞上发现了FLT3的表达。三色分析进一步表明，大多数CD34 FLT3+细胞高水平共表达CD117（KIT）。最后，在18/22例急性髓系白血病（AML）和3/5例B淋巴细胞系急性淋巴细胞白血病（ALL）的白血病原始细胞上发现了FLT3的表达，这为这些疾病的诊断和治疗提供了一种可能的应用。
