Page 198 - Haematologica Vol. 109 - July 2024

D. Shin et al. in multivariate analysis (Hazard Ratio [HR]=65.96, 95% Confi-
dence Interval [CI]: 2.06-2109.60), as indicated by the median survivals of 121.8 months in the low FLT3L group (N=22, ≤182 pg/mL) and 67.03 months in the high FLT3L group (N=21, >182 pg/mL) (Figure 1D). Interestingly, many clinical parameters, such as age, subtype of heavy and light chain, cytogenetics of hypo- and hyperdiploidy, anemia, hypercalcemia, azote- mia, and hypoalbuminemia, were not significantly associated with OS (Table 2). On the other hand, sex tended to show a marginal (P=0.078) correlation with survival in multivariate analysis, and International Staging System (ISS) advanced stage (III) was a poor prognostic factor compared to stage I (HR=3.85 and 813.31, 95% CI: 0.83-17.88 and 6.60-100259.2; P=0.086 and 0.006 in univariate and multivariate analyses,
Figure 2. Fms-like tyrosine kinase 3 ligand enhances Dick Kopf-related protein 1 expression via STAT3 signaling. (A) The mRNA expression of Dick Kopf-related protein 1 (DKK1) and Fms-like tyrosine kinase 3 ligand (FLT3L) obtained from HEK293T, HeLa, and U2OS cells treated with 40 ng/mL rhFLT3L for from two to approximately four days, as analyzed by quantitative real-time poly- merase chain reaction (RT-qPCR) (N=4). (B) Western blot analysis of phosphorylation of STAT3, total STAT3 and DKK1 under treat- ment with rhFLT3L (40 ng/mL) in HEK293T and MOLP8 cells for three days. (C) In HEK293T on treatment with rhFLT3L (40 ng/ mL), Stattic (10 μM), or both for three days, protein level of phosphorylated STAT3 and total STAT3 and mRNA level of DKK1 and FLT3L were analyzed by western blotting and RT-qPCR, respectively (N=8). Statistical analysis was performed by one-way ANOVA with Dunnett’s multiple comparison. Error bars indicate the standard deviation of 3 independent replicates. *P<0.05, **P<0.01, ***P<0.001, ns: not significant (P>0.05).
Haematologica | 109 July 2024
ARTICLE - FLT3L promotes osteolysis in multiple myeloma
logistic regression analysis using FLT3L as a bi-categorical dependent variable (≤182 pg/mL vs. >182 pg/mL) and clinical factors as independent variables in the treatment-naïve MM patients (N=43). This analysis showed that the percentages (%) of BM plasma cell and hyperdiploidy were significantly associated with FLT3L in MM (Online Supplementary Table S1), consistent with the finding in Figure 1B. This analysis suggests the associations of serum M-protein level and the presence of osteolytic lesions with FLT3L levels (P=0.071, 0.073, and 0.069, respectively). These data thus imply that these 4 factors may collectively contribute to FLT3L levels. We next examined the association of the FLT3L level with the OS of the 43 patients. The high level of FLT3L in BM (>182 pg/ mL) was significantly (P=0.018) associated with poor survival
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