Kuchenbauer Florian, Schoch Claudia, Kern Wolfgang, Hiddemann Wolfgang, Haferlach Torsten, Schnittger Susanne
Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig-Maximilians University of Munich, University Hospital Grosshadern, Munich, Germany.
Br J Haematol. 2005 Jul;130(2):196-202. doi: 10.1111/j.1365-2141.2005.05595.x.
In the present study 170 newly diagnosed acute promyelocytic leukaemia patients (M3: n = 121; M3v: n = 49) were molecularly characterised with respect to PML breakpoint and additional molecular mutations. In total, 83 patients were positive for bcr1 (49%), five for bcr2 (3%) and 82 for bcr3 (48%). Bcr3 was more frequent in M3v (65.3%) compared with M3 (41.3%) (P = 0.005). Cases with bcr3 showed a significantly higher white blood cell count (median: 3.65 x 10(9)/l vs. 1.59 x 10(9)/l, P = 0.003), as well as a higher PML-RARAABL expression ratio (14.8% vs. 72.7%, P < 0.005) compared with bcr1. FLT3-length-mutations were detected more frequently together with bcr3 compared with bcr1 (56.5% vs. 19.4%, P < 0.001) and in M3v compared with M3 (64.5% vs. 24.1%, P < 0.005). FLT3 tyrosine kinase mutations were found in eight cases (6.4%) and were distributed equally within the total group. Analysis for further mutations revealed no MLL-PTD and KIT mutations and only two cases of 99 analysed (2%) with NRAS mutations. FLT3-mutations were detected in 62 of 139 cases (44.6%) and associated with a significant lower overall survival (P = 0.0339). In addition, cases with bcr3 showed a tendency for a worse event-free survival (P = 0.0795) compared with the bcr1 group.
在本研究中，对170例新诊断的急性早幼粒细胞白血病患者（M3：n = 121；M3v：n = 49）进行了PML断点及其他分子突变的分子特征分析。总共83例患者bcr1呈阳性（49%），5例bcr2呈阳性（3%），82例bcr3呈阳性（48%）。与M3（41.3%）相比，bcr3在M3v中更常见（65.3%）（P = 0.005）。与bcr1相比，bcr3病例的白细胞计数显著更高（中位数：3.65×10⁹/L对1.59×10⁹/L，P = 0.003），以及PML-RARA ABL表达率更高（1十四点八%对72.7%，P < 0.005）。与bcr1相比，FLT3长度突变与bcr3同时检出的频率更高（56.5%对19.4%，P < 0.001），且在M3v中比M3更常见（64.5%对24.1%，P < 0.005）。在8例（6点4%）病例中发现了FLT3酪氨酸激酶突变，在整个组中分布均匀。进一步的突变分析未发现MLL-PTD和KIT突变，在99例分析病例中仅2例（2%）有NRAS突变。在139例病例中的62例（44.6%）检测到FLT3突变，且与总体生存率显著降低相关（P = 0.0339）。此外，与bcr1组相比，bcr3病例的无事件生存率有变差的趋势（P = 0.0795）。
