1 Department of Laboratory Medicine, Medical University of Vienna , Vienna, Austria .
Stem Cells Dev. 2013 Dec 1;22(23):3043-51. doi: 10.1089/scd.2013.0096. Epub 2013 Sep 4.
In vitro endogenous erythroid colony (EEC) formation is a common finding in BCR-ABL-negative myeloproliferative neoplasms. The aim of the present study was to determine the prevalence and the clinical significance of EEC growth in chronic myeloid leukemia (CML). Results of clonogeneic progenitor cell assays from 52 patients with newly diagnosed CML were correlated with disease characteristics at presentation and molecular response to imatinib. EECs (median 7 per dish, range 1-39) were detectable in 16 patients (31%). The proportion of patients with a high-risk Sokal score was lower in the EEC group (7% vs. 30%, respectively). The cumulative incidence of achieving a major molecular response after 2 years of imatinib was similar for both groups. However, patients with EECs were less likely to achieve a more profound decline of BCR-ABL transcripts. After 6 years of imatinib, the cumulative probability [95% CI] of reaching a ≥4 log reduction of BCR-ABL was 48% [16%; 92%] for patients of the EEC group and 84% [63%; 97%] for patients of the No EEC group. The probability [95% CI] of achieving a >4.5 log reduction of BCR-ABL after 7 years was 13% [2%; 61%] for patients with EECs and 52% [30%; 78%] for patients without EECs. In vitro EECs disappeared after achievement of a major molecular response in all evaluable patients. The data indicate that EEC formation is a recurrent finding in patients with CML which deserves further attention as a possible biomarker predicting the degree of molecular response to imatinib.
体外内源性红细胞集落 (EEC) 形成是 BCR-ABL 阴性骨髓增殖性肿瘤的常见现象。本研究旨在确定慢性髓性白血病 (CML) 中 EEC 生长的发生率和临床意义。对 52 例初诊 CML 患者的克隆性祖细胞检测结果与疾病特征和伊马替尼的分子反应相关联。在 16 例患者 (31%) 中可检测到 EEC(中位数为每皿 7 个,范围为 1-39)。EEC 组的高危 Sokal 评分患者比例较低 (分别为 7%和 30%)。两组患者在接受伊马替尼治疗 2 年后获得主要分子反应的累积发生率相似。然而,EEC 患者达到 BCR-ABL 转录物更显著下降的可能性较小。在接受伊马替尼治疗 6 年后,EEC 组患者达到 BCR-ABL 降低≥4 个对数的累积概率[95%CI]为 48%[16%;92%],而无 EEC 组患者的累积概率为 84%[63%;97%]。在接受伊马替尼治疗 7 年后,EEC 组患者达到 BCR-ABL 降低>4.5 个对数的概率为 13%[2%;61%],而无 EEC 组患者的概率为 52%[30%;78%]。在所有可评估患者中,获得主要分子反应后 EEC 消失。数据表明,EEC 形成是 CML 患者的一种复发性表现,值得进一步关注,作为预测伊马替尼分子反应程度的可能生物标志物。