The Clinical and Prognostic Significance of Ribonucleotide Reductase Subunits RRM1 and RRM2 mRNA Levels in Patients with Chronic Lymphocytic Leukemia.

Clinical Hematology International Pub Date : 2023-06-01 DOI:10.1007/s44228-023-00033-x

Sevastianos Chatzidavid, Christina-Nefeli Kontandreopoulou, Panagiotis T Diamantopoulos, Nefeli Giannakopoulou, Panagiota Katsiampoura, Christos Stafylidis, Georgios Dryllis, Marie-Christine Kyrtsonis, Maria Dimou, Panayiotis Panayiotidis, Nora-Athina Viniou

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Abstract

Ribonucleotide Reductase (RNR) converts ribonucleotides to deoxyribonucleotides required for DNA replication and repair. RNR consists of subunits M1 and M2. It has been studied as a prognostic factor in several solid tumors and in chronic hematological malignancies, but not in chronic lymphocytic leukemia (CLL). Peripheral blood samples were collected from 135 CLL patients. M1/M2 gene mRNA levels were measured and expressed as a RRM1-2/GAPDH ratio. M1 gene promoter methylation was studied in a patients' subgroup. M1 mRNA expression was higher in patients without anemia (p = 0.026), without lymphadenopathy (p = 0.005) and 17p gene deletion (p = 0.031). Abnormal LDH (p = 0.022) and higher Rai stage (p = 0.019) were associated with lower M1 mRNA levels. Higher M2 mRNA levels were found in patients without lymphadenopathy (p = .048), Rai stage 0 (p = 0.025) and Trisomy 12 (p = 0.025). The correlation between RNR subunits and clinic-biological characteristics in CLL patients demonstrate RNR's potential role as a prognostic factor.

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慢性淋巴细胞白血病患者核糖核苷酸还原酶亚基RRM1和RRM2 mRNA水平的临床及预后意义

核糖核苷酸还原酶(RNR)将核糖核苷酸转化为DNA复制和修复所需的脱氧核糖核苷酸。RNR由亚基M1和M2组成。它已被研究为几种实体瘤和慢性血液恶性肿瘤的预后因素，但在慢性淋巴细胞白血病(CLL)中没有。收集135例CLL患者外周血标本。测量M1/M2基因mRNA水平，并以RRM1-2/GAPDH比值表达。在患者亚组中研究了M1基因启动子甲基化。M1 mRNA在无贫血(p = 0.026)、无淋巴结病(p = 0.005)和17p基因缺失(p = 0.031)的患者中表达较高。LDH异常(p = 0.022)和Rai分期升高(p = 0.019)与M1 mRNA水平降低相关。M2 mRNA水平在无淋巴结病变(p = 0.048)、Rai分期(p = 0.025)和12三体(p = 0.025)患者中均较高。在CLL患者中，RNR亚基与临床生物学特征之间的相关性证明了RNR作为预后因素的潜在作用。

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Clinical Hematology International

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