Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Ann Hematol. 2014 Jun;93(6):977-82. doi: 10.1007/s00277-014-2061-9. Epub 2014 Apr 16.
Transforming mutations in RAS genes are commonly found in human malignancies, including myeloid leukemias. To investigate the incidence, spectrum, and distribution of activating K- and N-RAS mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients, 204 CN-AML patients were screened. Activating K- and N-RAS mutations were detected in 3 of 204 (1.5 %) and 22 of 204 (10.8 %) CN-AML samples, respectively. RAS mutated patients presented with a lower percentage of bone marrow blasts (65 vs 80 %, P = 0.022). RAS mutations tended to occur with nucleophosmin-1 (NPM1) mutations (P = 0.079), and all three samples containing K-RAS mutations had concomitant NPM1 mutations. There was no significant overlap between K-RAS mutations and N-RAS, FLT3, CEBPA, IDH1/2, WT1 or MLL mutations. RAS mutation status did not impact relapse-free or overall survival of CN-AML patients. In contrast to reports of noncanonical RAS mutations in other cancers, including some leukemia subtypes, we only observed K- and N-RAS mutations in codons 12, 13, or 61 in CN-AML samples. Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.
RAS 基因的转化突变在人类恶性肿瘤中很常见，包括髓系白血病。为了研究细胞遗传学正常的急性髓系白血病（CN-AML）患者中激活的 K-和 N-RAS 突变的发生率、谱和分布，对 204 例 CN-AML 患者进行了筛选。在 204 例 CN-AML 样本中，分别检测到 3 例（1.5%）和 22 例（10.8%）存在激活的 K-和 N-RAS 突变。RAS 突变患者的骨髓原始细胞比例较低（65%对 80%，P=0.022）。RAS 突变倾向于与核磷蛋白 1（NPM1）突变同时发生（P=0.079），且所有 3 例含 K-RAS 突变的样本均伴有 NPM1 突变。K-RAS 突变与 N-RAS、FLT3、CEBPA、IDH1/2、WT1 或 MLL 突变之间没有显著重叠。RAS 突变状态并不影响 CN-AML 患者的无复发生存或总生存。与其他癌症（包括一些白血病亚型）中非典型 RAS 突变的报告不同，我们仅在 CN-AML 样本中观察到 12、13 或 61 密码子的 K-和 N-RAS 突变。我们的研究结果表明，虽然 K-RAS 突变在 CN-AML 中不常见，但激活的 K-RAS 突变可能与突变型 NPM1 合作诱导白血病。
