Legras S, Günthert U, Stauder R, Curt F, Oliferenko S, Kluin-Nelemans H C, Marie J P, Proctor S, Jasmin C, Smadja-Joffe F
INSERM U268 Hôpital Paul-Brousse, Villejuif, France.
Blood. 1998 May 1;91(9):3401-13.
CD44 is a ubiquitous cell-surface glycoprotein that displays many variant isoforms (CD44v) generated by alternative splicing of exons 2v to 10v. The expression of variant isoforms is highly restricted and correlated with specific processes, such as leukocyte activation and malignant transformation. We have herein studied CD44v expression in acute myeloid leukemia (AML) and, for comparison, in normal myelopoiesis. Protein expression of total CD44 and of CD44-3v, -6v, and -9v isoforms has been measured using specific monoclonal antibodies and flow cytometry. The composition of variant exon transcripts has been analyzed by semi-quantitative reverse transcriptase-polymerase chain reaction followed by Southern hybridization with exon-specific probes. Our data show that (1) CD44-6v isoforms are expressed on 12.0% +/- 2.5% of normal CD34(+) cells; this expression is sharply upregulated through monopoiesis and, inversely, downregulated during granulopoiesis. Also, CD44-3v and CD44-9v isoforms are detected on 10% and 14% of normal monocytes, respectively. (2) Sixty-nine from a total of 95 AML patients display a variable proportion (range, 5% to 80%) of CD44-6v+ leukemic cells. (3) A shorter overall survival characterizes the group of AML patients displaying more than 20% of CD44-6v+ leukemic cells (8 months v 18 months, P < .02). These data suggest, for the first time, that the protein expression of CD44-6v containing isoforms may serve as a new prognostic factor in AML.
CD44是一种普遍存在的细胞表面糖蛋白，它具有许多由外显子2v至10v可变剪接产生的变异体同种型（CD44v）。变异体同种型的表达受到高度限制，并与特定过程相关，如白细胞激活和恶性转化。我们在此研究了急性髓系白血病（AML）中CD44v的表达，并与正常骨髓生成进行比较。使用特异性单克隆抗体和流式细胞术检测了总CD44以及CD44 - 3v、- 6v和- 9v同种型的蛋白表达。通过半定量逆转录聚合酶链反应，随后用外显子特异性探针进行Southern杂交，分析了变异外显子转录本的组成。我们的数据表明：（1）CD44 - 6v同种型在12.0%±2.5%的正常CD34(+)细胞上表达；这种表达在单核细胞生成过程中急剧上调，相反，在粒细胞生成过程中下调。此外，分别在10%和14%的正常单核细胞上检测到CD44 - 3v和CD44 - 9v同种型。（2）95例AML患者中有69例显示出不同比例（范围为5%至80%）的CD44 - 6v+白血病细胞。（3）AML患者中CD44 - v6+白血病细胞超过20%的组总体生存期较短（8个月对18个月，P < 0.02）。这些数据首次表明，含CD44 - 6v的同种型蛋白表达可能是AML的一种新的预后因素。
