Department of Molecular Biotechnology and Health Sciences, Section of Pathology, University of Turin, Turin, Italy.
Oncol Rep. 2013 May;29(5):1867-72. doi: 10.3892/or.2013.2328. Epub 2013 Mar 5.
Core binding factor (CBF) acute myeloid leukaemia (AML) represents 5-8% of all AMLs and has a relatively favourable prognosis. However, activating c-KIT mutations are reported to be associated with higher risk of relapse and shorter survival. To verify the incidence and prognostic value of c-KIT mutations in CBF AML, we retrospectively analysed bone marrow samples of 23 consecutive adult patients with de novo CBF AML [14 inv(16) and 9 t(8;21)] treated at a single institution from 2000 to 2011. All patients received standard induction chemotherapy with cytarabine, idarubicin and etoposide; 13 underwent allogeneic stem cell transplantation. c-KIT mutations in exons 8, 9, 10, 11, 13, 14 and 17 were assessed by PCR amplification in combination with direct sequencing. c-KIT mutations (3 in exon 10 and 4 in exon 17) were detected in 7/23 (30.4%) patients, 3 with t(8;21) and 4 with inv(16). No difference in c-KIT mutation status was observed between cases with inv(16) or t(8;21) alone and cases with additional cytogenetic abnormalities. No association between gender, age, white blood cell and platelet count, peripheral blood and bone marrow blast cells at diagnosis, achievement of complete remission, cytogenetic risk groups and Wilms tumour gene 1 (WT1) levels was found. On the contrary, lactate dehydrogenase (LDH) values were higher in mutated than in non-mutated patients (p=0.01). Overall survival (OS) rates were longer in CBF compared to the other types of AML and disease-free survival (DFS) was longer in inv(16) than in t(8;21) AML. OS and DFS were similar in mutated and non-mutated CBF AML patients. Our results confirm a better prognosis for CBF AML than all other AML categories, and for inv(16) than t(8;21) AML. However, no prognostic value for c-KIT mutational status was found in our series. The association between LDH levels and c-KIT mutation would indicate a more active proliferation for mutated CBF AML.
核心结合因子（CBF）急性髓系白血病（AML）占所有 AML 的 5-8%，预后相对较好。然而，激活的 c-KIT 突变与更高的复发风险和更短的生存时间相关。为了验证 CBF AML 中 c-KIT 突变的发生率和预后价值，我们回顾性分析了 2000 年至 2011 年在单一机构接受治疗的 23 例初发 CBF AML 成人患者（14 例 inv(16)和 9 例 t(8;21)）的骨髓样本。所有患者均接受阿糖胞苷、伊达比星和依托泊苷标准诱导化疗；13 例行异基因造血干细胞移植。通过聚合酶链反应扩增结合直接测序评估 c-KIT 外显子 8、9、10、11、13、14 和 17 中的突变。在 23 例患者中检测到 7 例（30.4%）存在 c-KIT 突变（10 号外显子 3 例，17 号外显子 4 例），其中 3 例为 t(8;21)，4 例为 inv(16)。单独存在 inv(16)或 t(8;21)与存在其他细胞遗传学异常的病例之间，c-KIT 突变状态无差异。c-KIT 突变与性别、年龄、白细胞和血小板计数、外周血和骨髓原始细胞、完全缓解的获得、细胞遗传学风险组和 Wilms 瘤基因 1（WT1）水平无关。相反，突变患者的乳酸脱氢酶（LDH）值高于非突变患者（p=0.01）。与其他 AML 类型相比，CBF 的总生存率（OS）更高，与 t(8;21) AML 相比，inv(16)的无病生存率（DFS）更高。在突变和非突变 CBF AML 患者中，OS 和 DFS 相似。我们的结果证实，与所有其他 AML 类型相比，CBF AML 的预后更好，与 t(8;21) AML 相比，inv(16)的预后更好。然而，我们的研究未发现 c-KIT 突变状态具有预后价值。LDH 水平与 c-KIT 突变之间的关联表明，突变的 CBF AML 增殖更活跃。
