【venetoclax +阿扎胞苷方案对携带MYC基因扩增双分钟染色体的AML患者的细胞遗传学反应】。

Fumiaki Fujii, Shingo Nojima, Satomi Matsuoka, Yasutaka Kakinoki
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摘要

双分钟染色体(dmin)是一种小的、无中心的染色体外片段,经常介导癌基因扩增,诱导疾病快速进展,预后不良,尽管在髓系肿瘤中并不常见。一位81岁妇女因贫血和血小板减少症住院。骨髓检查显示54.0%的原细胞。她被诊断为急性髓性白血病(法、美、英分类,M2;世界卫生组织分类,急性髓性白血病(AML),未另行说明,AML伴成熟)。染色体分析显示46例患者背景中存在3-45 dmin, 20例中期患者中有14例存在XX。光谱核型分析表明,该基因来源于8号染色体。针对MYC基因的荧光原位杂交(FISH)表明,dmins含有全长MYC基因,具有多个信号。最后,她通过MYC扩增被诊断为AML伴dmin,并给予venetoclax加阿扎胞苷化疗。两个疗程后,FISH未发现MYC扩增信号,表明患者处于细胞遗传学缓解状态。目前,她已经完成了四个疗程的治疗,病情完全缓解。Venetoclax联合阿扎胞苷可能是通过MYC扩增治疗急性髓性白血病预后不良的有效方案。
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[Prompt cytogenetic response by venetoclax plus azacitidine regimen in a patient with AML harboring double-minute chromosomes with MYC gene amplification].

Double minute chromosomes (dmin) are small, acentric, and extrachromosomal fragments that frequently mediate oncogene amplification and induce rapid disease progression with poor prognosis, although they are infrequent in myeloid neoplasms. An 81-year-old woman with anemia and thrombocytopenia was admitted to our hospital. Bone marrow examination showed 54.0% of the blasts. She was diagnosed with acute myeloid leukemia (French-American-British classification, M2; World Health Organization classification, acute myeloid leukemia [AML], not otherwise specified, AML with maturation). Chromosomal analysis revealed the presence of 3-45 dmin in the background of 46 and XX in 14 out of 20 metaphases examined. Spectral karyotyping examination demonstrated that the dmins were derived from chromosome 8. Fluorescence in situ hybridization (FISH) targeting the MYC gene demonstrated that dmins contained full-length MYC genes with multiple signals. Finally, she was diagnosed with AML with dmin via MYC amplification and was administered with venetoclax plus azacitidine chemotherapy. After two cycles of the regimen, FISH found no MYC amplification signals, indicating her state being in cytogenetic remission. At present, she has finished four cycles of the regimen and remained in complete remission. Venetoclax plus azacitidine could be an effective regimen for the poor prognosis of AML with dmin through MYC amplification.

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