Expression of the WNT Family Genes in Multiple Myeloma Patients with Different Chemotherapy Response

NI Enukashvili1,2,3, LA Belik1,2,3, II Kostroma1, NYu Semenova1, VA Balashova1, DV Baram1, SV Gritsaev1, SS Bessmeltsev1, SV Sidorkevich1, IS Martynkevich1

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

2 Institute of Cytology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064

3 Pokrovskii Cell Technology Center, 85 Bolshoi pr-t V.O., Saint Petersburg, Russian Federation, 1949106

For correspondence: Natella Iosifovna Enukashvili, PhD in Biology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; Tel.: +7(965)085-93-25; e-mail: natellae@gmail.com

For citation: Enukashvili NI, Belik LA, Kostroma II, et al. Expression of the WNT Family Genes in Multiple Myeloma Patients with Different Chemotherapy Response. Clinical oncohematology. 2023;16(3):294–302. (In Russ).

DOI: 10.21320/2500-2139-2023-16-3-294-302


ABSTRACT

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.

Keywords: multiple myeloma, WNT signaling pathway, hematopoietic niche, mesenchymal stromal cells, prognostic markers.

Received: January 5, 2023

Accepted: May 27, 2023

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