单中心109例慢性粒单核细胞白血病患者的分子特征
[Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center].
作者信息
Qu S Q, Pan L J, Qin T J, Xu Z F, Li B, Wang H J, Sun Q, Jia Y J, Li C W, Cai W Y, Gao Q Y, Jiao M, Xiao Z J
机构信息
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2023 May 14;44(5):373-379. doi: 10.3760/cma.j.issn.0253-2727.2023.05.004.
To explore the molecular features of chronic myelomonocytic leukemia (CMML) . According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (=4.129, 95% 1.481-11.510, =0.007) and TET2 (=5.276, 95% 1.979-14.065, =0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (=0.174, 95% 0.038-0.791, =0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old 47 years old, <0.001), white blood cell count (15.9×10(9)/L 4.4×10(9)/L, <0.001), proportion of monocytes (21.5% 15%, =0.001), and hemoglobin level (86 g/L 74 g/L, =0.014). TET2 mutations (=0.021) and SRSF2 mutations (=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
为探究慢性粒单核细胞白血病（CMML）的分子特征。根据2022年世界卫生组织（WHO 2022）分类标准，对2016年3月至2021年10月期间的113例CMML患者和840例骨髓增生异常综合征（MDS）患者进行重新分类，并分析CMML患者的临床和分子特征。在113例CMML患者中，23例（20.4%）被重新诊断为急性髓系白血病（AML），其中18例为伴有NPM1突变的AML，3例为伴有KMT2A重排的AML，2例为伴有MECOM重排的AML。其余90例患者符合WHO 2022 CMML标准。此外，840例MDS患者中有19例（2.3%）符合WHO 2022 CMML标准。99%的CMML患者检测到至少一种基因突变，突变中位数为4个。突变频率≥10%的基因有：ASXL1（48%）、NRAS（34%）、RUNX1（33%）、TET2（28%）、U2AF1（23%）、SRSF2（21.1%）、SETBP1（20%）、KRAS（17%）、CBL（15.6%）和DNMT3A（11%）。配对分析显示，SRSF2常与ASXL1共同突变（=4.129，95% 1.481 - 11.510，=0.007）和TET2共同突变（=5.276，95% 1.979 - 14.065，=0.001）。SRSF2和TET2常见于老年（≥60岁）的骨髓增殖性CMML（MP - CMML）患者。U2AF1突变常与TET2相互排斥（=0.174，95% 0.038 - 0.791，=0.024），且常见于年轻（<60岁）的骨髓增生异常性CMML（MD - CMML）患者。与绝对单核细胞计数（AMoC）≥1×10⁹/L和<1×10⁹/L的患者相比，前者的发病年龄中位数更高（60岁对47岁，<0.001）、白细胞计数更高（15.9×10⁹/L对4.4×10⁹/L，<0.001）、单核细胞比例更高（21.5%对15%，=0.001）以及血红蛋白水平更高（86 g/L对74 g/L，=0.014）。TET2突变（=0.021）和SRSF2突变（=0.011）在AMoC≥1×10⁹/L的患者中更常见，而U2AF1突变（<0.001）在AMoC<1×10⁹/L的患者中更常见。两组之间其他基因突变频率无显著差异。根据WHO 2022分类，近20%的CMML患者在诊断时AMoC<1×10⁹/L，且MD - CMML和MP - CMML具有不同的分子特征。
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