Ohler L, Berer A, Aletaha D, Kabrna E, Heinze G, Streubel B, Fonatsch C, Haas O A, Lechner K, Geissler K
Department of Internal Medicine I, University of Vienna, Vienna, Austria.
Br J Haematol. 2001 Apr;113(1):120-5. doi: 10.1046/j.1365-2141.2001.02698.x.
We have analysed the results of semi-solid bone marrow cultures in 296 patients with de novo acute myeloblastic leukaemia (AML) and correlated them with the leukaemic karyotype. A favourable prognostic karyotype was found in 52 patients (group A, 18.3%), an intermediate karyotype in 163 patients (group B, 57.4%), and unfavourable cytogenetics were observed in 69 patients (group C, 24.3%). Median colony growth according to the three risk groups was 2 (range 0--344) in group A, 14.5 (range 0--5000) in group B and 50.0 (0--3000) in group C (A vs. B, P < 0.001; A vs. C, P < 0.001; B vs. C, P < 0.01). Among the patients treated with chemotherapy (n = 257), median colony growth was 10 (range 0-5000) in those who achieved complete remission (CR) compared with 56.5 (range 0-1000) in patients without remission (NR) (P = 0.002). The median colony growth of all patients [13/10(5) bone marrow mononuclear cells (BMMCs); range 0--5000] significantly discriminated between patients regarding survival (OS 11 vs. 7 months, P = 0.044). However, multiple Cox regression analysis revealed cytogenetic risk groups as the most important predictor for achieving CR, disease-free and overall survival, with colony growth adding no additional prognostic information. In 64 patients, colony growth was also investigated without the addition of exogenous cytokines. Interestingly, none of the patients with a favourable karyotype exhibited autonomous growth, whereas 50% with an intermediate and 73% of patients with an unfavourable karyotype displayed either partial or full autonomous growth in vitro (P = 0.0004). Our data suggest that the growth potential of the leukaemic clone seems to be critically influenced by the molecular changes emerging from chromosomal abnormalities.
我们分析了296例初发急性髓细胞白血病（AML）患者的半固体骨髓培养结果，并将其与白血病核型相关联。52例患者（A组，18.3%）具有良好的预后核型，163例患者（B组，57.4%）具有中等核型，69例患者（C组，24.3%）观察到不良细胞遗传学特征。根据三个风险组，A组的集落生长中位数为2（范围0 - 344），B组为14.5（范围0 - 5000），C组为50.0（0 - 3000）（A组与B组比较，P < 0.001；A组与C组比较，P < 0.001；B组与C组比较，P < 0.01）。在接受化疗的257例患者中，达到完全缓解（CR）的患者集落生长中位数为10（范围0 - 5000），而未缓解（NR）的患者为56.5（范围0 - 1000）（P = 0.002）。所有患者的集落生长中位数[13/10(5)骨髓单个核细胞（BMMCs）；范围0 - 5000]在患者生存方面有显著差异（总生存期11个月对7个月，P = 0.044）。然而，多因素Cox回归分析显示，细胞遗传学风险组是实现CR、无病生存期和总生存期的最重要预测因素，集落生长并未增加额外的预后信息。在64例患者中，还研究了未添加外源性细胞因子时的集落生长情况。有趣的是，具有良好核型的患者均未表现出自主生长，而具有中等核型的患者中有50%以及具有不良核型的患者中有73%在体外表现出部分或完全自主生长（P = 0.0004）。我们的数据表明，白血病克隆的生长潜力似乎受到染色体异常所产生的分子变化的严重影响。
