DE Morais Guilherme Passos, Machado Caio Bezerra, Dias Nogueira Beatriz Maria, DE Pinho Pessoa Flávia Melo Cunha, DE Sousa Oliveira Deivide, Ribeiro Rodrigo Monteiro, DA Silva Jean Breno Silveira, Seabra Aline Damasceno, Mello Júnior Fernando Augusto Rodrigues, Burbano Rommel Rodriguez, Khayat André Salim, DE Moraes Filho Manoel Odorico, DE Moraes Maria Elisabete Amaral, Moreira-Nunes Caroline Aquino
Unichristus University Center, Faculty of Biomedicine, Fortaleza, Brazil.
Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
Cancer Diagn Progn. 2024 Sep 1;4(5):592-598. doi: 10.21873/cdp.10368. eCollection 2024 Sep-Oct.
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.
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.
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.
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.
背景/目的:尽管相互易位t(9;22)(q34;q11)是慢性髓性白血病(CML)的一个标志,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。根据基因的断点,有可能获得三种异构体,其中p190因其出现时所诱导的不良预后而引人注目。由于BCR::ABL1诱导的基因组不稳定,有人提出扩大聚-ADP-核糖聚合酶-1(PARP1)及其抑制剂在血液系统肿瘤中的应用。
我们使用TaqMan®通过定量实时PCR(qPCR)测量PARP1的表达水平,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。
我们发现PARP1在ALL、AML和CML中的表达不同,并且p190转录本在这些人群中不遵循线性模式。我们还发现PARP1表达与年龄、白细胞和p190转录本数量无关。
尽管所分析的变量之间缺乏统计学相关性,但鉴于这种易位所促进的不稳定情况,PARP1在BCR::ABL1白血病中的作用不能排除。最后,需要进一步开展涉及更大患者样本的研究,以及对可能影响不同BCR::ABL1白血病亚型发病机制的其他分子途径进行研究。