Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia.
Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia.
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CSF3R、SRSF2和SETBP1突变在慢性中性粒细胞白血病和慢性粒单核细胞白血病中的临床意义。
DOI：
10.18632/oncotarget.15355
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发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Zhang SJ
中科院分区：
文献类型：
--
作者：
Ouyang Y;Qiao C;Chen Y;Zhang SJ
慢性中性粒细胞白血病（CNL）和慢性粒单核细胞白血病（CMML）是罕见的血液肿瘤。我们对 10 名 CNL 和 56 名 CMML 患者进行了 CSF3R、SRSF2 和 SETBP1 突变分析。在该样本队列中，80%的 CNL 患者携带 CSF3R 突变，其中 CSF3R T618I 突变占主导地位。 7.1%和5.3%的CMML患者分别发现CSF3R和SETBP1突变，而25%的CMML患者携带SRSF2突变。引人注目的是，我们发现在 CMML 患者中检测到的所有 CSF3R 突变均以 P733T 突变为代表。 CSF3R P733T 突变代表一种新的 CSF3R 突变。此外，四名 CSF3R P733T 突变患者均未携带 SRSF2 突变 [CSF3R P733T 和 SRSF2 联合突变患者为 0/14 (0%)，而 CSF3R P733T 和 wt SRSF2 联合突变患者为 4/42 (9.5%)，P < 0.001]。与 wt SRSF2（均 P < 0.001）和 wt SETBP1（分别为 P < 0.001 和 P = 0.02）患者相比，mut SRSF2 和 mut SETBP1 患者的总生存期 (OS) 和无进展生存期 (PFS) 较短。虽然我们发现 CSF3R 突变状态导致 OS 和 PFS 没有显着差异，但我们的工作表明 CSF3R T618I 突变是一种对 CNL 具有良好特异性和敏感性的诊断标志物。总之，我们的研究强调了中国人群中 CNL 和 CMML 患者的有效诊断和预后标志物。
Chronic neutrophilic leukemia (CNL) and chronic myelomonocytic leukemia (CMML) are rare hematologic neoplasms. We performed CSF3R, SRSF2 and SETBP1 mutational analyses in 10 CNL and 56 CMML patients. In this sample cohort, 80% of CNL patients harbored CSF3R mutations, of which the CSF3R T618I mutation was dominant. Mutations in CSF3R and SETBP1 were found in 7.1% and 5.3% CMML patients respectively, while 25% of CMML patients carried SRSF2 mutations. Strikingly, we identified that all of the CSF3R mutations detected in CMML patients were represented by a P733T mutation. The CSF3R P733T mutation represents a novel CSF3R mutation. In addition, none of the four CSF3R P733T mutated patients carried SRSF2 mutations [0/14 (0%) patients with combined CSF3R P733T and SRSF2 mutations vs. 4/42 (9.5%) with CSF3R P733T and wt SRSF2, P < 0.001]. Both mut SRSF2 and mut SETBP1 patients had shorter overall survival (OS) and progression-free survival (PFS) compared to patients with wt SRSF2 (P < 0.001 both) and wt SETBP1 (P < 0.001 and P = 0.02, respectively). While we found no significant differences in OS and PFS as a consequence of CSF3R mutation status, our work suggest that the CSF3R T618I mutation is a diagnostic marker with good specificity and sensitivity for CNL. In conclusion, our study highlights effective diagnostic and prognostic markers of CNL and CMML patients in the Chinese population.