Receiver-operating characteristic (ROC) curve for median apparent diffusion coefficient.

Receiver-operating characteristic (ROC) curve for median apparent diffusion coefficient.</p

Comparison of MRI-derived indices according to their response to mobilization.

Comparison of MRI-derived indices according to their response to mobilization.</p

Predictive factors significantly associated with relatively poor mobilization by multivariate analysis.

Predictive factors significantly associated with relatively poor mobilization by multivariate analysis.</p

Representative whole-body diffusion-weighted imaging (DWI) for the patient classifications of mobilizer and relatively poor mobilizer.

Left image, mobilizer: Whole-body DWI of a 47-year-old man with symptomatic myeloma who had an adequate number of collected CD34+ cells (4.4×106 CD34+ cells/kg). Median ADC of the total diffusion volume was 0.78×10−3 mm2/s. Right image, relatively poor mobilizer: Whole-body DWI of a 59-year-old woman with symptomatic myeloma who had an inadequate number of collected CD34+ cells (3.8×106 CD34+ cells/kg). Median ADC of the total diffusion volume was 1.53×10−3 mm2/s.</p

MRI sequence protocol.

IntroductionHigh-dose chemotherapy followed by autologous stem cell transplant is the mainstay of treatment for multiple myeloma (MM). The purpose of this study was to evaluate the ability of MRI-derived indices to predict mobilized hematopoietic stem cell yield.Materials and methodsIn this exploratory pilot work, we retrospectively analyzed 38 mobilization procedures for MM. Successful mobilization procedure was defined as a total yield of >4.0×106 CD34+ cells/kg. Univariate and multivariate analyses were performed to identify factors with a significant effect on successful mobilization from among clinical characteristics including number of prior lines of therapy, period from diagnosis to harvest, type of monoclonal protein (M protein); and radiological characteristics including total diffusion volume (tDV), median apparent diffusion coefficient (ADC) of tDV, and mean fat fraction of bone marrow calculated by MRI.ResultsUnivariate analyses showed that relatively poor mobilization was significantly associated with M protein of Bence-Jones type and with median ADC of tDV (P = 0.02 and P = 0.004, respectively). Multivariate analyses using these two indices showed that median ADC of tDV was a significant predictive factor for adequate mobilization (P = 0.01), with an area under the curve of 0.784 (cutoff value, 1.18×10−3 mm2/s; sensitivity, 72.7%; specificity, 87.5%).ConclusionThe present data indicate that median ADC of tDV is a predictive factor for relatively poor mobilization of hematopoietic stem cells in MM patients undergoing autologous stem cell transplant.</div

Clinical information for six cases who plerixafor was given.

Clinical information for six cases who plerixafor was given.</p

Semi-automated segmentation of myeloma lesions and measurement of fat fraction on MR images.

(A) Coronal maximum intensity projection image acquired by diffusion-weighted imaging with a computed b-value of 1000 s/mm2. For estimation of whole-body volumetric tumor burden by measurement of apparent diffusion coefficient (ADC), voxels showing an ADC between 0.55 ×10−3 and 2.0 ×10−3 mm2/s are extracted (indicated in orange) as an estimate of total diffusion volume, as a surrogate marker for tumor burden. (B) Coronal fat fraction map obtained by modified Dixon Quant sequence. The region of interest (white rectangle) for measuring fat fraction is placed on the L3 vertebral body on a midcoronal image. The region of interest cannot be placed from L1 to L3 on a single image because the mid-coronal level of each vertebral body is different due to lumbar lordosis.</p

Patient characteristics and biochemistry results.

IntroductionHigh-dose chemotherapy followed by autologous stem cell transplant is the mainstay of treatment for multiple myeloma (MM). The purpose of this study was to evaluate the ability of MRI-derived indices to predict mobilized hematopoietic stem cell yield.Materials and methodsIn this exploratory pilot work, we retrospectively analyzed 38 mobilization procedures for MM. Successful mobilization procedure was defined as a total yield of >4.0×106 CD34+ cells/kg. Univariate and multivariate analyses were performed to identify factors with a significant effect on successful mobilization from among clinical characteristics including number of prior lines of therapy, period from diagnosis to harvest, type of monoclonal protein (M protein); and radiological characteristics including total diffusion volume (tDV), median apparent diffusion coefficient (ADC) of tDV, and mean fat fraction of bone marrow calculated by MRI.ResultsUnivariate analyses showed that relatively poor mobilization was significantly associated with M protein of Bence-Jones type and with median ADC of tDV (P = 0.02 and P = 0.004, respectively). Multivariate analyses using these two indices showed that median ADC of tDV was a significant predictive factor for adequate mobilization (P = 0.01), with an area under the curve of 0.784 (cutoff value, 1.18×10−3 mm2/s; sensitivity, 72.7%; specificity, 87.5%).ConclusionThe present data indicate that median ADC of tDV is a predictive factor for relatively poor mobilization of hematopoietic stem cells in MM patients undergoing autologous stem cell transplant.</div

The rs2275913 SNP results in differential binding of NFAT.

<p>(A) The location of the rs2275913 SNP within the promoter region of the IL-17 gene. The underlined sequence corresponds to the oligomers used in EMSA assay. The NFAT binding sites <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026229#pone.0026229-Liu1" target="_blank">[21]</a> are indicated in red and by red boxes. (B) IL-17 probes were allowed to interact with nuclear extracts from PHA-PBMCs in an EMSA assay. Lane 1, free probes; lane 2, biotin-labeled probes plus nuclear extracts; lane 3, biotin-labeled probes plus nuclear extracts plus a 50-fold molar excess of unlabeled probes. The figure shown is representative of five independent experiments. (C) IL-17 probes were allowed to interact with recombinant NFAT proteins in an EMSA assay. Lane 1, free probes; lane 2, biotin-labeled probes plus GST-NFAT; lane 3, biotin-labeled probes plus GST-NFAT plus a 50-fold molar excess of unlabeled probes; lane 4, biotin-labeled probes plus GST-NFAT plus a 50-fold molar excess of unlabeled oligomers containing a NFAT consensus site. The figure shown is representative of five independent experiments. (D) The intensity of the bands corresponding to the DNA/protein interaction (lane 2 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026229#pone-0026229-g004" target="_blank"><b>Fig. 4C</b></a>) were evaluated by densitometry to compare the binding affinity of the 197A allele and 197G allele for recombinant NFAT. The values are represented as arbitrary units (au). **indicates <i>P</i><0.01.</p

The modulation of the reporter gene expression by the rs2275913 SNP.

<p>(A) PHA-PBMCs were transfected with a luciferase expression vector alone (pGL3-Luc) or with a luciferase expression vector containing fragments of the IL-17 promoter with the 197A or 197G alleles (IL-17/A-Luc and IL-17/G-Luc). The transfected cells were cultured for 48 hr, and firefly luciferase activities were measured and normalized to Renilla luciferase. (B) The PHA-PBMCs were transfected as described above. Twenty four hours after transfection, the cells were treated with anti-CD3 and anti-CD28 mAbs or with CsA, and cultured for other 24 hr. The firefly luciferase activities were measured and normalized to Renilla luciferase. The values represent the normalized levels +/− S.E.M. from five independent experiments. *indicates <i>P</i><0.05 and **<i>P</i><0.01.</p