Paar Christian, Herber Gabriele, Voskova Daniela, Fridrik Michael, Stekel Herbert, Berg Jörg
Institute of Laboratory Medicine, General Hospital Linz, Krankenhausstrasse 9, A-4020, Linz, Austria.
Mol Cytogenet. 2013 Sep 30;6(1):40. doi: 10.1186/1755-8166-6-40.
Acute myeloid leukemia (AML) comprises a spectrum of myeloid malignancies which are often associated with distinct chromosomal abnormalities, and the analysis of such abnormalities provides us with important information for disease classification, treatment selection and prognosis. Some chromosomal abnormalities albeit recurrent are rare such as tetrasomy 8 or isochromosome 5p. In addition, erratic chromosomal rearrangements may occur in AML, sometimes unbalanced and also accompanied by other abnormalities. Knowledge on the contribution of rare abnormalities to AML disease, progression and prognosis is limited.Here we report a unique case of acute monoblastic leukemia with gain of i(5)(p10), tetrasomy 8, an unbalanced translocation der(19)t(17;19)(q23;p13.3) and mutated NPM1.
Bone marrow cells were examined by conventional karyotyping, fluorescence in situ hybridization (FISH) and mutation analysis at diagnosis and follow-up. At diagnosis we detected trisomy 8, an unbalanced translocation der(19)t(17;19)(q23;p13.3) and mutated NPM1. During the course of the disease we observed clonal evolution with gain of i(5)(p10), tetrasomy 8 and eventually duplication of der(19)t(17;19)(q23;p13.3). By using the der(19)t(17;19) as clonal marker, we found that i(5)(p10) and tetrasomy 8 were secondary genetic events and that tetrasomy 8 had clonally evolved from trisomy 8.
This case of acute monoblastic leukemia presents a combination of rare chromosomal abnormalities including the unbalanced translocation der(19)t(17;19)(q23;p13.3), hitherto un-reported in AML. In addition, our case supports the hypothesis of a step-wise clonal evolution from trisomy 8 to tetrasomy 8 in AML. Reporting and collecting data of rare chromosomal abnormalities will add information to AML disease, progression and prognosis, and may eventually translate to improved patient management.
急性髓系白血病（AML）包含一系列髓系恶性肿瘤，这些肿瘤常与不同的染色体异常相关，对这些异常的分析为我们提供了疾病分类、治疗选择和预后的重要信息。一些染色体异常虽然常见但很罕见，如8号染色体四体或5号染色体短臂等臂染色体。此外，AML中可能会出现不稳定的染色体重排，有时是不平衡的，还伴有其他异常。关于罕见异常对AML疾病、进展和预后的作用的了解有限。在此，我们报告一例独特的急性单核细胞白血病病例，伴有i(5)(p10)增加、8号染色体四体、不平衡易位der(19)t(17;19)(q23;p13.3)以及NPM1突变。
在诊断和随访时，通过常规核型分析、荧光原位杂交（FISH）和突变分析对骨髓细胞进行了检查。诊断时，我们检测到8号染色体三体、不平衡易位der(19)t(17;19)(q23;p13.3)以及NPM1突变。在疾病过程中，我们观察到克隆进化，伴有i(5)(p10)增加、8号染色体四体，最终der(19)t(17;19)(q23;p13.）重复。通过将der(19)t(17;19)用作克隆标记，我们发现i(5)(p10)和8号染色体四体是继发的遗传事件，并且8号染色体四体是从8号染色体三体克隆进化而来的。
该例急性单核细胞白血病呈现出罕见染色体异常的组合，包括不平衡易位der(19)t(17;19)(q23;p13.3)，这在AML中迄今尚未见报道。此外，我们的病例支持AML中从8号染色体三体到8号染色体四体逐步克隆进化的假说。报告和收集罕见染色体异常的数据将为AML疾病、进展和预后增加信息，并最终可能转化为改善患者管理。
