Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
J Clin Lab Anal. 2022 Apr;36(4):e24289. doi: 10.1002/jcla.24289. Epub 2022 Feb 17.
The present study aimed to explore the changes in the expressions of six tumor-related genes in myeloproliferative neoplasms (MPNs). The study population included 130 patients with MPNs (52 with chronic myeloid leukemia (CML), 49 with essential thrombocythemia (ET), 20 with polycythemia vera (PV), and 9 with primary myelofibrosis (PMF)) and 51 healthy individuals.
The expression profiling of six genes (ADAMTS18, CMTM5, CDKN2B, DCC, FHIT, and WNT5B) in the peripheral blood granulocyte cells was explored by real-time quantitative reverse transcription polymerase chain reaction.
The patients with MPNs showed significant downregulation of CMTM5 (EFC = 0.66) and DCC (EFC = 0.65) genes in contrast to a non-significant upregulation of ADAMTS18, CDKN2B, FHIT, and WNT5B genes. Downregulation of DCC was consistent in all subtypes of MPN (EFC range: 0.591-0.860). However, CMTM5 had a 1.22-fold upregulation in PMF in contrast to downregulation in other MPN subtypes (EFC range: 0.599-0.775). The results revealed a significant downregulation in CMTM5 and DCC at below 60-years of age. Furthermore, female patients showed a clear-cut downregulation in both CMTM5 and DCC (EFC DCC: 0.436 and CMTM5: 0.570), while male patients presented a less prominent downregulation with a borderline p-value only in DCC (EFC: 0.69; p = 0.05).
Chronic myeloid leukemia cases showed a significant upregulation of WNT5B, as a known oncogenesis gene. Two tumor suppressor genes, namely DCC and CMTM5, were downregulated in the patients with MPNs, especially in females and patients below 60 years of age.
本研究旨在探讨骨髓增殖性肿瘤（MPN）中六种肿瘤相关基因表达的变化。研究人群包括 130 例 MPN 患者（52 例慢性髓性白血病（CML），49 例特发性血小板增多症（ET），20 例真性红细胞增多症（PV）和 9 例原发性骨髓纤维化（PMF））和 51 名健康个体。
通过实时定量逆转录聚合酶链反应（qRT-PCR）探索外周血粒细胞中六种基因（ADAMTS18、CMTM5、CDKN2B、DCC、FHIT 和 WNT5B）的表达谱。
与 ADAMTS18、CDKN2B、FHIT 和 WNT5B 基因的非显著上调相比，MPN 患者的 CMTM5（EFC=0.66）和 DCC（EFC=0.65）基因明显下调。DCC 的下调在所有 MPN 亚型中均一致（EFC 范围：0.591-0.860）。然而，CMTM5 在 PMF 中上调 1.22 倍，而在其他 MPN 亚型中下调（EFC 范围：0.599-0.775）。结果表明，CMTM5 和 DCC 在 60 岁以下的患者中明显下调。此外，女性患者的 CMTM5 和 DCC 均明显下调（EFC DCC：0.436 和 CMTM5：0.570），而男性患者的下调程度较轻，仅在 DCC 时具有边缘 p 值（EFC：0.69；p=0.05）。
慢性髓性白血病病例中，已知致癌基因 WNT5B 明显上调。两种肿瘤抑制基因，即 DCC 和 CMTM5，在 MPN 患者中下调，尤其是在女性和 60 岁以下的患者中。
