Burillo-Sanz S, Morales-Camacho R M, Caballero-Velázquez T, Vargas M T, García-Lozano J R, Falantes J F, Prats-Martín C, Bernal R, Pérez-Simón J A
Servicio de Inmunología, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Department of Hematology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Int J Lab Hematol. 2016 Feb;38(1):64-71. doi: 10.1111/ijlh.12435. Epub 2015 Sep 29.
Chromosomal rearrangements involving NUP98 gene have been associated with human leukemias such as de novo AML, therapy-related AML (t-AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Genetic fusion NUP98-HOXA9, caused by t(7;11)(p15;p15), is a recurrent cytogenetic alteration in de novo acute myeloid leukemia (AML) usually found in young Asian patients and its description in therapy-related myeloid neoplasms (t-MN) is rare. Only one Asian case with molecular demonstration of the NUP98-HOXA9 fusion has been reported in therapy-related leukemia. NUP98-HOXA9 leukemogenic mechanism is derived from the transcription factor activity of the chimeric protein, which enhances the expression of genes related to cellular differentiation arrest and proliferation.
We studied a Caucasian woman with a therapy-related acute myeloid leukemia after Ewing's sarcoma. Molecular demonstration of the genetic fusion NUP98-HOXA9 was performed by RT-PCR, and gene expression was analyzed by real-time PCR, including four AML patients with MLL rearrangements for comparative analysis. Cytologic and flow cytometric analysis was also carried out.
After cytologic and flow cytometric analysis diagnostics was therapy-related myeloid neoplasm (t-MN). The major component of blasts in the acute leukemia was with neutrophilic differentiation, but 13% erythroid lineage blasts were also found. Cytogenetic and FISH analysis revealed t(7;11)(p15;p15) and NUP98-HOXA9 fusion gene was demonstrated. Gene expression analysis showed upregulation of EVI1 and MEIS1 in the index patient, both of them previously related to a worst outcome.
In this work, we include a detailed molecular, clinical, cytological, and cytometric study of the second t-AML bearing NUP98-HOXA9 genetic fusion.
涉及NUP98基因的染色体重排与人类白血病有关，如原发性急性髓系白血病（AML）、治疗相关急性髓系白血病（t-AML）、骨髓增生异常综合征（MDS）和慢性髓系白血病（CML）。由t(7;11)(p15;p15)导致的基因融合NUP98-HOXA9是原发性急性髓系白血病（AML）中一种常见的细胞遗传学改变，通常见于年轻的亚洲患者，而其在治疗相关髓系肿瘤（t-MN）中的描述很少。在治疗相关白血病中，仅报道过1例有分子证据证实NUP98-HOXA9融合的亚洲病例。NUP98-HOXA9白血病发生机制源于嵌合蛋白的转录因子活性，该活性增强了与细胞分化停滞和增殖相关基因的表达。
我们研究了1例患尤因肉瘤后发生治疗相关急性髓系白血病的白种女性。通过逆转录聚合酶链反应（RT-PCR）对基因融合NUP98-HOXA9进行分子鉴定，并通过实时聚合酶链反应分析基因表达，包括4例有MLL重排的AML患者用于比较分析。还进行了细胞学和流式细胞术分析。
经过细胞学和流式细胞术分析，诊断为治疗相关髓系肿瘤（t-MN）。急性白血病中原始细胞的主要成分呈嗜中性分化，但也发现了13%的红系原始细胞。细胞遗传学和荧光原位杂交（FISH）分析显示存在t(7;11)(p15;p15)，并证实了NUP98-HOXA9融合基因。基因表达分析显示该指数患者中EVI1和MEIS1上调，这两个基因此前均与较差的预后相关。
在本研究中，我们对第二例携带NUP98-HOXA9基因融合的t-AML进行了详细的分子、临床、细胞学和细胞计量学研究。
