| Jiaming Li,Sujiang Zhang. Gene mutations in a patient with chronic myelomonocytic leukemia and changes upon progression to acute myeloid leukemia and during treatment. Oncol Transl Med, 2019, 5: 30-32. |
| CMML患者基因突变及其向AML转化和治疗后的变化 |
| Gene mutations in a patient with chronic myelomonocytic leukemia and changes upon progression to acute myeloid leukemia and during treatment |
| Received:November 17, 2018 Revised:March 21, 2019 |
| DOI：10.1007/s10330-018-0318-8 |
| 中文关键词: 慢性粒细胞白血病，急性髓系白血病，突变，地西他滨，硼替佐米，血小板，SETD2，LILB4 |
| 英文关键词: chronic myelomonocytic leukemia; acute myeloid leukemia; mutation; decitabine; bortezomib; platelets; SETD2; LILRB4 |
| 基金项目:Supported by a grant from the Foundation of Ruijin Hospital North Affiliated with Shanghai Jiao Tong University School of Medicine (No. 2018ZY03). |
| Author Name | Affiliation | E-mail | | Jiaming Li | Ruijin Hospital North Affiliated with Shanghai Jiao Tong University School of Medicine | lijiaming007007@126.com | | Sujiang Zhang* | Ruijin Hospital North Affiliated with Shanghai Jiao Tong University School of Medicine | zhangsjb1181@126.com |
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| 中文摘要: |
| 慢性粒细胞白血病(CMML)是一种罕见的恶性血液病，具有骨髓增生异常综合征(MDS)和骨髓增生性肿瘤的重叠特征，并且高风险向急性髓系白血病(AML)转化。本研究报告了一例M蛋白阳性的CMML患者，通过追踪连续骨髓样本中突变基因的基因频率(VAF)，阐述CMML向急性髓细胞白血病(AML)转化进程中及应用地西他滨(DAC)联合硼替佐米(Bortezomib)治疗后基因克隆的变化。首先，我们观察到不同的基因克隆对化疗的敏感性和突变不完全清除可能与低应答率和疗效短暂相关。第二，DAC不能阻止治疗中新的遗传改变和遗传损伤的积累，从而导致CMML急性转化。最后，我们发现免疫功能紊乱可进一步推动CMML向AML克隆演化。总之，在CMML进展或治疗下突变和克隆结构的变化可以预测CMML预后，从分子水平为患者寻找最佳的个体化治疗策略。 |
| 英文摘要: |
| Objective Chronic myelomonocytic leukemia (CMML) has been categorized as an uncommon
hematological malignancy with overlapping features of myelodysplastic syndromes (MDS) and
myeloproliferative neoplasms that have an inherent risk of progressing to acute myeloid leukemia (AML).
Methods This study presents a case of confirmed CMML combined with M protein, in which the molecular
changes upon progression to AML and under decitabine (DAC) plus bortezomib therapy were reported by
tracking variant allele frequency (VAF) of mutations in a series of bone marrow samples.
Results First, variable sensitivity of clones was observed during DAC treatment, and incomplete mutation
clearance may be associated with low overall response rate and unsustained response. Secondly, DAC
cannot prevent the new genetic alterations and accumulation of genetic progression on treatment, leading
to acute transformation. Finally, autoimmunity was found to have acted as an important pathogenetic factor,
increasing the additive mutations that further drive the clonal evolution in CMML.
Conclusion Overall, changes in mutations and clonal architecture during CMML progression or treatment
are predictive of an early evaluation of therapeutic strategies in CMML. |
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