多发性骨髓瘤患者对抗肿瘤治疗有不同反应的WNT基因表达

Натэлла Иосифовна Енукашвили, Л. А. Белик, И. И. Кострома, Н. Ю. Семенова, В. А. Балашова, Д. В. Барам, С. В. Грицаев, С. С. Бессмельцев, С. В. Сидоркевич, И. С. Мартынкевич
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 Materials & Methods. The study enrolled 12 MM patients aged 49–71 years (the median age 61 years) after standard induction bortezomib therapy. The treatment efficacy was assessed in accordance with the criteria of International Myeloma Working Group (IMWG). Patients were stratified in groups with complete and partial response (CPR; group 1, n = 9) and no response (group 2, n = 3). Besides, a group of primary untreated patients was formed (n = 2). The control group included healthy donors of BM (n = 3). The levels of the WNT and CTNNB1 gene expression were assessed by real-time PCR on cDNA isolated from MSC.
 Results. In the group of 2 primary patients, two genes (WNT2B and WNT9B) considerably differed in the degree of expression. In non-responders (n = 3), the WNT2B expression could not be determined, whereas the WNT15 expression appeared to be increased. In group CPR (n = 9), mRNA level of the WNT5A gene increased after therapy, whereas the WNT3A gene expression returned to the normal level. The WNT7B gene transcription level did not differ in the control and comparison groups. In group CPR, a significant expression increase in the β-catenin-coding CTNNB1 gene was detected.
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摘要

的目标。比较多发性骨髓瘤(MM)患者骨髓(BM)造血生态位间充质基质细胞(MSC)中WNT家族基因的表达水平。 材料,方法。该研究招募了12名接受标准诱导硼替佐米治疗的MM患者,年龄49-71岁(中位年龄61岁)。按照国际骨髓瘤工作组(IMWG)的标准评估治疗效果。患者被分为完全缓解和部分缓解组(CPR;1组,n = 9)和无反应组(2组,n = 3),另设未治疗组(n = 2),对照组为健康BM供者(n = 3),采用MSC分离cDNA实时荧光定量PCR检测WNT和CTNNB1基因表达水平。结果。在2例原发患者中,两个基因(WNT2B和WNT9B)的表达程度存在显著差异。在无应答者(n = 3)中,无法确定WNT2B的表达,而WNT15的表达似乎有所增加。在CPR组(n = 9),治疗后WNT5A基因mRNA水平升高,而WNT3A基因表达恢复正常水平。WNT7B基因转录水平在对照组和对照组中没有差异。在CPR组中,β-连环蛋白编码基因CTNNB1的表达显著增加。 结论。WNT2B、WNT9B和CTNNB1基因表达的差异表明,它们有可能作为MM的预后分子标志物。
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Экспрессия генов семейства WNT у больных множественной миеломой с различным ответом на противоопухолевую терапию
Aim. To compare the expression levels of the WNT family genes in mesenchymal stromal cells (MSC) of the bone marrow (BM) hematopoietic niche in multiple myeloma (MM) patients vs. healthy donors. Materials & Methods. The study enrolled 12 MM patients aged 49–71 years (the median age 61 years) after standard induction bortezomib therapy. The treatment efficacy was assessed in accordance with the criteria of International Myeloma Working Group (IMWG). Patients were stratified in groups with complete and partial response (CPR; group 1, n = 9) and no response (group 2, n = 3). Besides, a group of primary untreated patients was formed (n = 2). The control group included healthy donors of BM (n = 3). The levels of the WNT and CTNNB1 gene expression were assessed by real-time PCR on cDNA isolated from MSC. Results. In the group of 2 primary patients, two genes (WNT2B and WNT9B) considerably differed in the degree of expression. In non-responders (n = 3), the WNT2B expression could not be determined, whereas the WNT15 expression appeared to be increased. In group CPR (n = 9), mRNA level of the WNT5A gene increased after therapy, whereas the WNT3A gene expression returned to the normal level. The WNT7B gene transcription level did not differ in the control and comparison groups. In group CPR, a significant expression increase in the β-catenin-coding CTNNB1 gene was detected. Conclusion. The differences identified in the expression of the WNT2B, WNT9B, and CTNNB1 genes suggest the possibility of their use as prognostic molecular markers in MM.
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CiteScore
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12 weeks
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