Kant A M, Advani S H, Zingde S M
Molecular Biology Laboratory, Cancer Research Institute, Parel, Mumbai, India.
Leuk Res. 1997 Mar;21(3):225-34. doi: 10.1016/s0145-2126(96)00118-x.
Morphologically mature granulocytes from patients with chronic myeloid leukemia exhibit a defect in receptor mediated endocytosis of FITC-conjugated heat-aggregated IgG. In our earlier studies, we have shown that transcripts for Fc gammaRII and Fc gammaRIII are lowered in CML granulocytes, while no such trend was seen for CD11b, CD18 and actin, the other molecules involved in this process. We have also shown by flow cytometry that the number of granulocytes expressing the Fc receptors on their surface is lowered in CML patients. In this report, we show that the lowered steady state level of the mRNA for the Fc receptors is due to their faster degradation and not due to any defect in transcription. A study of the expression of mRNA for Fc gammaRIII in morphologically mature CML granulocytes by in situ hybridization showed that there is heterogeneity in the expression of this receptor, with some cells positive for the message and some not. These results suggest that the Fc gammaRIII transcript reaches a stable RNA pool in only some of the granulocytes, whereas in the rest of the cells, it is probably degraded after it is transcribed and is therefore not detected. The Fc gammaRIII is probably one of the first antigens to be lost from the leukemic granulocyte surface during the transition of the disease from the chronic phase to the accelerated phase and finally to the blast crisis.
慢性髓性白血病患者形态学成熟的粒细胞在受体介导的异硫氰酸荧光素（FITC）偶联的热聚集IgG内吞作用中存在缺陷。在我们早期的研究中，我们发现慢性髓性白血病粒细胞中FcγRII和FcγRIII的转录本水平降低，而参与此过程的其他分子CD11b、CD18和肌动蛋白则未出现这种趋势。我们还通过流式细胞术表明，慢性髓性白血病患者表面表达Fc受体的粒细胞数量减少。在本报告中，我们表明Fc受体mRNA的稳态水平降低是由于其降解速度加快，而非转录存在任何缺陷。通过原位杂交对形态学成熟的慢性髓性白血病粒细胞中FcγRIII mRNA表达的研究表明，该受体的表达存在异质性，一些细胞的信息呈阳性，而一些细胞则呈阴性。这些结果表明，FcγRIII转录本仅在部分粒细胞中进入稳定的RNA池，而在其余细胞中，它可能在转录后被降解，因此未被检测到。在疾病从慢性期转变为加速期并最终发展为急变期的过程中，FcγRIII可能是白血病粒细胞表面最早丢失的抗原之一。
