Association of PARP1 Expression Levels and Clinical Parameters in Different Leukemic Subtypes With BCR::ABL1 p190+ Translocation.

Guilherme Passos DE Morais, Caio Bezerra Machado, Beatriz Maria Dias Nogueira, Flávia Melo Cunha DE Pinho Pessoa, Deivide DE Sousa Oliveira, Rodrigo Monteiro Ribeiro, Jean Breno Silveira DA Silva, Aline Damasceno Seabra, Fernando Augusto Rodrigues Mello Júnior, Rommel Rodriguez Burbano, André Salim Khayat, Manoel Odorico DE Moraes Filho, Maria Elisabete Amaral DE Moraes, Caroline Aquino Moreira-Nunes
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Abstract

Background/aim: Although the reciprocal translocation t(9;22)(q34;q11) is a hallmark of chronic myeloid leukemia (CML), it is also present in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Depending on the gene's breakpoint, it is possible to obtain three isoforms, among which p190 stands out for the poor prognosis it induces whenever it appears. Due to the genomic instability induced by BCR::ABL1, it is proposed to expand the applicability of poly-ADP-ribose polymerase-1 (PARP1) and its inhibitors in hematological neoplasms.

Materials and methods: We measured the expression levels of PARP1 by quantitative real-time PCR (qPCR) using TaqMan®, correlating its expression with BCR::ABL1 p190+, to evaluate its influence in the clinic of adult patients.

Results: We found that PARP1 is expressed differently in ALL, AML and CML and that p190 transcripts do not follow a linear pattern in these populations. We also found that PARP1 expression is not correlated with age, white blood cell and the amount of p190 transcripts.

Conclusion: Despite the lack of statistical correlation between the variables analyzed, the role of PARP1 in BCR::ABL1 leukemia cannot be ruled out, given the instability profile promoted by this translocation. Finally, further studies involving a larger sample of patients are needed, as well as investigations into other molecular pathways that may impact on the pathogenesis of different BCR::ABL1 leukemic subtypes.

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带有 BCR::ABL1 p190+ 转位的不同白血病亚型中 PARP1 表达水平与临床参数的关系
背景/目的:虽然t(9;22)(q34;q11)互变是慢性髓性白血病(CML)的特征,但它也存在于急性淋巴细胞白血病(ALL)和急性髓性白血病(AML)中。根据基因断点的不同,有可能出现三种异构体,其中 p190 尤为突出,因为它的出现会导致不良预后。由于BCR::ABL1诱导的基因组不稳定性,建议扩大聚ADP核糖聚合酶-1(PARP1)及其抑制剂在血液肿瘤中的应用:我们采用 TaqMan® 实时定量 PCR(qPCR)技术测定了 PARP1 的表达水平,并将其表达与 BCR::ABL1 p190+ 相关联,以评估其在成年患者临床中的影响:结果:我们发现,PARP1 在 ALL、AML 和 CML 中的表达不同,p190 转录本在这些人群中的表达也不呈线性模式。我们还发现,PARP1 的表达与年龄、白细胞和 p190 转录本的数量无关:结论:尽管所分析的变量之间缺乏统计学相关性,但鉴于这种易位所导致的不稳定性,不能排除PARP1在BCR::ABL1白血病中的作用。最后,还需要对更多的患者样本进行进一步研究,并对可能影响不同BCR::ABL1白血病亚型发病机制的其他分子途径进行调查。
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