Yang Ruqing, Jiang Minghua, Zhao Junzhao, Chen Hui, Gong Jian, You Yaying, Song Laiyue, Li Zhen, Li Qian
Reproductive Medicine Center, Department of Gynaecology and Obstetrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China,
Cancer Manag Res. 2019 Feb 15;11:1559-1567. doi: 10.2147/CMAR.S189025. eCollection 2019.
Near-triploidy/tetraploidy is rarely found in acute leukemia. Only limited data are available to characterize this condition, and it remains largely unknown.
In our study, we performed karyotype analysis on 1,031 patients diagnosed with acute leukemia from 2006 to 2018. A total of 10 patients of near-triploidy/tetraploidy karyotype were enrolled. Two cases of near-triploidy (66-79 chromosomes) and eight cases of near-tetraploidy (84-100 chromosomes) were identified. Bone marrow samples of these 10 patients were analyzed by fluorescence in situ hybridization with 19 commercially available probes that detected a small portion of gene alterations and large regions of chromosome amplifications.
Of the six patients with acute myelocytic leukemia, we detected three cases of double t(8;21)(q22;q22) that have not been previously reported, and one of them demonstrated ins(21;8) (q22;q24q22). We also describe a novel pediatric case carrying double t(15;17)(q22;q21) and receiving targeted treatment with all-trans retinoic acid therapy. To date, this case has responded well to the regimen and has shown continuous complete remission. All patients received chemotherapy. One of them received allogeneic hematopoietic stem cell transplant (HSCT) and survived for 22 months. Eight of the 10 patients died, and the median overall survival was 11 months.
Using fluorescence in situ hybridization, we identified the distinct complex karyotype of near-triploidy/tetraploidy and provided further prognostic information. Tetraploidy acute promyelocytic leukemia had favorable prognosis; thus, HSCT was not necessary. The case of insertion t(21;8)(q22;q24q22) in tetraploidy responded poorly to chemotherapy and achieved molecular remission with difficultly. Data from patients in this group indicated that near-triploidy/tetraploidy acute leukemia has poor prognosis and new therapy is urgently needed.
近三倍体/四倍体在急性白血病中很少见。仅有有限的数据可用于描述这种情况，而且其在很大程度上仍不为人所知。
在我们的研究中，我们对2006年至2018年诊断为急性白血病的1031例患者进行了核型分析。共纳入10例近三倍体/四倍体核型患者。鉴定出2例近三倍体（66 - 79条染色体）和8例近四倍体（84 - 100条染色体）。用19种市售探针通过荧光原位杂交分析这10例患者的骨髓样本，这些探针可检测一小部分基因改变和大片段染色体扩增。
在6例急性髓细胞白血病患者中，我们检测到3例此前未报道的双t(8;21)(q22;q22)，其中1例表现为ins(21;8) (q22;q24q22)。我们还描述了1例携带双t(15;17)(q22;q21)的儿童新病例，该病例接受了全反式维甲酸靶向治疗。迄今为止，该病例对治疗方案反应良好，持续完全缓解。所有患者均接受了化疗。其中1例接受了异基因造血干细胞移植（HSCT），存活22个月。10例患者中有8例死亡，中位总生存期为11个月。
通过荧光原位杂交，我们鉴定出近三倍体/四倍体独特的复杂核型，并提供了进一步的预后信息。四倍体急性早幼粒细胞白血病预后良好；因此，无需进行HSCT。四倍体中插入t(21;8)(q22;q24q22)的病例对化疗反应不佳，难以实现分子缓解。该组患者的数据表明，近三倍体/四倍体急性白血病预后不良，迫切需要新的治疗方法。
