Wafa Abdulsamad, ALmedania Suher, Aljapawe Abdulmunim, Liehr Thomas, Soulaiman Soulaiman E, Mouna Raja, Othman Moneeb A K, ALachkar Walid
1Department of Molecular Biology and Biotechnology, Human Genetics Division, Atomic Energy Commission, Damascus, Syria.
2Department of Molecular Biology and Biotechnology, Mammalians Biology Division, Atomic Energy Commission, Damascus, Syria.
BMC Hematol. 2018 Aug 31;18:21. doi: 10.1186/s12878-018-0114-3. eCollection 2018.
Chromosomal abnormalities are diagnostic and prognostic key factors in acute myeloid leukemia (AML) patients, as they play a central role for risk stratification algorithms. High hyperdiploidy (HH), a rare cytogenetic abnormality seen commonly in elder male AML patients, is normally categorized under AML with complex karyotype (CK). Accordingly, patients with HH generally are associated with low remission rates and a short overall survival.
Here we report a case of 21-year-old female, diagnosed with a de novo AML-M1 according to WHO classification and a CK at diagnosis. Cytogenetic, molecular cytogenetic approaches (standard fluorescence in situ hybridization (FISH), array-proven multicolor banding (aMCB)) and high resolution array comparative genomic hybridization (aCGH) analyses revealed a unique complex but still near diploid karyotype involving eleven chromosomes was identified. It included pentasomy 4, three yet unreported chromosomal aberrations t(1;2)(p35;p22), t(1;3)(p36.2;p26.2), and t(10;12)(p15.2;q24.11), and a combination of two cytogenetic events, yet unreported to appear in together, i.e. a reciprocal translocation t(1;3)(p36.2;p26.2) leading to / gene fusion, and monoallelic loss of tumor suppressor gene . After successful chemotherapeutic treatment the patient experienced a relapse to AML-M1, and she developed secondary AML-M6 with tetraploidy and HH. Unfortunately, the young woman died 8.5 months after initial diagnosis.
To the best of our knowledge, a comparable adult AML associated with such a CK, coexistence of 3q rearrangements with loss of at diagnosis, and HH in secondary AML were not previously reported. Thus, the combination of the here seen chromosomal aberrations in adult primary AML seems to indicate for an adverse prognosis.
染色体异常是急性髓系白血病（AML）患者诊断和预后的关键因素，因为它们在风险分层算法中起着核心作用。高超二倍体（HH）是一种罕见的细胞遗传学异常，常见于老年男性AML患者，通常归类于伴有复杂核型（CK）的AML。因此，HH患者通常缓解率低，总生存期短。
我们在此报告一例21岁女性，根据世界卫生组织分类诊断为初发AML-M1，诊断时为CK。细胞遗传学、分子细胞遗传学方法（标准荧光原位杂交（FISH）、阵列验证多色带分析（aMCB））和高分辨率阵列比较基因组杂交（aCGH）分析显示，发现了一种独特的复杂但仍接近二倍体的核型，涉及11条染色体。其中包括4号染色体五体、3种尚未报道的染色体畸变t(1;2)(p35;p22)、t(1;3)(p36.2;p26.2)和t(10;12)(p15.2;q24.11)，以及两种细胞遗传学事件的组合，这两种事件尚未报道同时出现，即导致//基因融合的相互易位t(1;3)(p36.2;p26.2)和肿瘤抑制基因的单等位基因缺失。成功化疗后，患者复发为AML-M1，并发展为伴有四倍体和HH的继发性AML-M6。不幸的是，这位年轻女性在初次诊断后8.5个月死亡。
据我们所知，此前尚未报道过与这种CK相关的类似成人AML、诊断时3q重排与//缺失并存以及继发性AML中的HH。因此，成人原发性AML中此处所见的染色体畸变组合似乎预示着不良预后。
