DNA修复基因表达与骨髓增生异常综合征中的骨髓细胞密度相关。

DNA repair gene expressions are related to bone marrow cellularity in myelodysplastic syndrome.

作者信息

Ribeiro Howard L, Maia Allan Rodrigo S, de Oliveira Roberta Taiane G, Costa Marília Braga, Farias Izabelle Rocha, de Paula Borges Daniela, de Sousa Juliana Cordeiro, Magalhães Silvia Maria M, Pinheiro Ronald F

机构信息

Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil.

Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil.

出版信息

J Clin Pathol. 2017 Nov;70(11):970-980. doi: 10.1136/jclinpath-2016-204269. Epub 2017 May 29.

DOI:10.1136/jclinpath-2016-204269

PMID:28554891

Abstract

OBJECTIVE

To evaluate the expression of genes related to nuclear excision (, and ), homologous recombination and non-homologous end-joining (, , and ) repair mechanisms, using quantitative PCR methodologies, and it relation with bone marrow cellularity in myelodysplastic syndrome (MDS).

METHODS AND RESULTS

A total of 51 adult de novo patients with MDS (3 refractory anaemia (RA), 11 refractory anaemia with ringed sideroblasts (RARS), 28 refractory cytopenia with multilineage dysplasia (RCMD), 3 refractory anaemia with excess blasts type I (RAEB-I), 5 refractory anaemia with excess blasts type II (RAEB-II), and 1 chronic myelomonocytic leukaemia (CMML) were evaluated. For karyotype, 16.2% patients were defined as very low prognosis, 59.5% low risk, 8.1% intermediate risk, 5.4% high risk and 10.8% very high risk. For bone marrow cellularity, 17.6%, 17.6% and 64.7% presented as hypocellular, normocellular and hypercellular, respectively. Patients with hypocellular MDS had significantly decreased expression of (p=0.000) (p=0.014), (p=0.003) (p=0.004) and (p=0.000) than those with normocellular/hypercellular bone marrow, whereas (p=0.049) and (p=0.000) genes were increased. In patients with hypoplastic MDS, a low expression of (p=0.0268), (p=0.0199) and (p=0.0493) was significantly associated with the presence of chromosomal abnormalities. We detected positive correlations between and (r=0.416; p=0.007), and (r=0.472; p=0.001), and (r=0.333; p=0.026), and (r=0.334; p=0.025), and (r=0.377; p=0.008), and (r=0.287; p=0.046), and (r=0.371; p=0.007) and and genes (r=0.895; p=0.0000). We also found among all patients evaluated that correlation with occurred most often.

CONCLUSIONS

These correlations demonstrate the important intrinsic relations between single and double DNA strand breaks genes in MDS, emphasising that these genes are related to MDS pathogenesis.

摘要

目的

采用定量聚合酶链反应方法评估与核切除（、和）、同源重组及非同源末端连接（、、和）修复机制相关基因的表达情况，及其与骨髓增生异常综合征（MDS）患者骨髓细胞计数的关系。

方法与结果

共评估了51例成年初发MDS患者（3例难治性贫血（RA）、11例环形铁粒幼细胞性难治性贫血（RARS）、28例多系发育异常的难治性血细胞减少症（RCMD）、3例I型原始细胞增多的难治性贫血（RAEB-I）、5例II型原始细胞增多的难治性贫血（RAEB-II）以及1例慢性粒单核细胞白血病（CMML））。就核型而言，16.2%的患者被定义为极低预后，59.5%为低危，8.1%为中危，5.4%为高危，10.8%为极高危。就骨髓细胞计数而言，分别有17.6%、17.6%和64.7%的患者表现为细胞减少、细胞计数正常和细胞增多。与骨髓细胞计数正常/增多的患者相比，细胞减少的MDS患者的表达显著降低（p = 0.000）（p = 0.014）、（p = 0.003）（p = 0.004）和（p = 0.000），而（p = 0.049）和（p = 0.000）基因表达增加。在发育不全的MDS患者中，（p = 0.0268）、（p = 0.0199）和（p = 0.0493）的低表达与染色体异常的存在显著相关。我们检测到与（r = 0.416；p = 0.007）、与（r = 0.472；p = 0.001）、与（r = 0.333；p = 0.026）、与（r = 0.334；p = 0.025）、与（r = 0.377；p = 0.008）、与（r = 0.287；p = 0.046）、与（r = 0.371；p = 0.007）以及与基因（r = 0.895；p = 0.0000）之间存在正相关。我们还发现在所有评估患者中，与的相关性最为常见。