scholarly journals Quantitative Imaging and Radiomics in Multiple Myeloma: A Potential Opportunity?

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 94
Author(s):  
Alberto Stefano Tagliafico ◽  
Alida Dominietto ◽  
Liliana Belgioia ◽  
Cristina Campi ◽  
Daniela Schenone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Medical Imaging ◽  
Bone Disease ◽  
Quantitative Methods ◽  
Quantitative Imaging ◽  
High Variability ◽  
Elderly Subjects ◽  
Bone Lesions ◽  
Imaging Data ◽  
Lytic Bone Lesions

Multiple Myeloma (MM) is the second most common type of hematological disease and, although it is rare among patients under 40 years of age, its incidence rises in elderly subjects. MM manifestations are usually identified through hyperCalcemia, Renal failure, Anaemia, and lytic Bone lesions (CRAB). In particular, the extent of the bone disease is negatively related to a decreased quality of life in patients and, in general, bone disease in MM increases both morbidity and mortality. The detection of lytic bone lesions on imaging, especially computerized tomography (CT) and Magnetic Resonance Imaging (MRI), is becoming crucial from the clinical viewpoint to separate asymptomatic from symptomatic MM patients and the detection of focal lytic lesions in these imaging data is becoming relevant even when no clinical symptoms are present. Therefore, radiology is pivotal in the staging and accurate management of patients with MM even in early phases of the disease. In this review, we describe the opportunities offered by quantitative imaging and radiomics in multiple myeloma. At the present time there is still high variability in the choice between various imaging methods to study MM patients and high variability in image interpretation with suboptimal agreement among readers even in tertiary centers. Therefore, the potential of medical imaging for patients affected by MM is still to be completely unveiled. In the coming years, new insights to study MM with medical imaging will derive from artificial intelligence (AI) and radiomics usage in different bone lesions and from the wide implementations of quantitative methods to report CT and MRI. Eventually, medical imaging data can be integrated with the patient’s outcomes with the purpose of finding radiological biomarkers for predicting the prognostic flow and therapeutic response of the disease.

scholarly journals Quantitative Imaging and Radiomics in Multiple Myeloma: opportunity or hype?

2020 ◽  
Author(s):  
Alberto Stefano Tagliafico ◽  
Alida Dominietto ◽  
Liliana Belgioia ◽  
Cristina Campi ◽  
Daniela Schenone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Medical Imaging ◽  
Bone Disease ◽  
Quantitative Methods ◽  
Quantitative Imaging ◽  
High Variability ◽  
Bone Lesions ◽  
Imaging Data ◽  
Lytic Bone Lesions ◽  
Ct And Mri

Multiple Myeloma (MM) is the second most common type of hematological disease and, although it is rare among patients under 40 years of age, its incidence rises in elderly subject. MM manifestations are usually known with the abbreviation CRAB (hyperCalcemia, Renal failure, Anaemia, and lytic Bone lesions). In particular, the extent of the bone disease is negatively related to a decreased patients’ quality of life and, in general, bone disease in MM increases both morbidity and mortality. The detection of lytic bone lesions on imaging, especially CT and MRI, is becoming crucial from the clinical viewpoint to separate asymptomatic from symptomatic MM patients and the detection of focal lytic lesion in these imaging data is becoming relevant even when no clinical symptoms are present. Therefore, radiology is pivotal in the staging and accurate management of patients with MM even in early phases of the disease. In this review we describe the opportunities offered by quantitative imaging and radiomics in multiple myeloma. At present time there is still high variability in the choice between various imaging methods to study MM patients and high variability in image interpretation with suboptimal agreement among readers even in tertiary centres. Therefore, the potential of medical imaging for patients affected by MM is still to be completely unveiled. In the next years, new insights to study MM with medical imaging will derive from artificial intelligence (AI) and radiomics usage in different bone lesions and from the wide implementations of quantitative methods to report CT and MRI. Eventually, medical imaging data can be integrated with the patient's outcomes with the purpose to find radiological biomarkers for predicting the disease prognostic flow and its therapeutic response.

Role of 18f-FDG PET/CT in the Management of Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3492-3492
Author(s):  
Elena Zamagni ◽  
Cristina Nanni ◽  
Patrizia Tosi ◽  
Stefano Fanti ◽  
Delia Cangini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Fdg Pet ◽  
Bone Lesions ◽  
Pet Ct ◽  
Lytic Bone Lesions ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Ct And Mri

Abstract Multiple myeloma (MM) is a malignant plasma cell disorder which involves the skeleton in more than 80% of patients at diagnosis. For almost four decades bone lesions have traditionally been detected by Whole Body X-Ray (WBXR) survey. Over the last years, newer methods of evaluation have been increasingly used for the detection of MM bone disease, including magnetic resonance imaging (MRI) of the spine. In comparison with WBXR, MRI has proven to be more sensitive, although its partial field of view (FOV) is a main limitation in clinical practice. 18F-FDG PET/CT is a non invasive and total body imaging method that may be usefully employed to explore bones and soft tissues in MM, to assess the degree and extent of active MM bone disease, as well as to evaluate response to therapy by distinguishing between active and inactive bone lesions. Aim of the present study was to compare WBXR survey, MRI and 18F-FDG PET/CT scanning in a series of 28 consecutive patients with newly diagnosed MM. Moreover, we compared post-treatment evaluation with MRI and 18F-FDG PET/CT with clinical response in 14/28 patients who received double autologous transplantation as up-front therapy for MM. All patients underwent WBXR, MRI and 18F-FDG PET/CT at baseline and 3 months after the second transplantation. Findings of 18 F-FDG PET/CT were compared to those of WBXR and MRI with respect to number and site of detected bone lesions. Results of comparison of 18 F-FDG PET/CT with WBXR at diagnosis were as follows: in 16/28 pts (57%) 18 F-FDG PET/CT detected more lesions, all of whom were located in the skeleton; notably, 9 of these 16 patients had a completely negative WBXR survey. In 12/28 pts (43%) both methods were superimposable. Results of comparison of 18 F-FDG PET/CT with MRI at diagnosis were as follows: in 7/28 pts (25%), 18 F-FDG PET/CT detected more lytic bone lesions which were all located out of the FOV of MRI (6 bone lesions, 1 soft tissue lesion); in 13/28 pts (46%) 18 F-FDG PET/CT and MRI detected the same number of lesions in the spine and pelvis; in 8/28 pts (29%) MRI detected an infiltrative pattern of the spine, without evidence of lytic lesions, whereas 18 F-FDG PET/CT was negative. Results of comparison of post-transplantation 18 F-FDG PET/CT and MRI with clinical response were as follows: 5 out of 12 patients with negative 18 F-FDG PET/CT were in clinical CR and the remaining 7 patients were in 3 PR. Only 7 out of 12 patients with negative 18 F-FDG PET/CT had normal MRI. In summary, in 57% of patients at diagnosis 18 F-FDG PET/CT was more sensitive than WBXR for the detection of lytic bone lesions. MRI of the spine was superior over 18 F-FDG PET/CT in 29% of patients, particularly with a diffuse bone marrow replacement. Based on these data, it can be concluded that careful evaluation of MM bone disease at diagnosis should include both MRI of the spine and 18 F- FDG PET/CT. More data are needed to understand the role of 18 F-FDG PET/CT in assessing response to treatment.

Heparanase Expression Correlates with Bone Destruction in the Patients with Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1813-1813 ◽  
Author(s):  
Shi Wei ◽  
Racquel Innis-Shelton ◽  
Li Nan ◽  
Jian Ruan ◽  
Rebecca S Sollie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Bone Marrow Cells ◽  
Bone Destruction ◽  
Bone Lesions ◽  
Bone Marrow Biopsies ◽  
Myeloma Cells ◽  
Lytic Bone Lesions ◽  
Marrow Cells

Abstract Abstract 1813 Multiple myeloma is an incurable malignancy, and excessive bone destruction is a major cause of morbidity in myeloma patients. However, the biologic mechanisms involved in the pathogenesis of myeloma-induced bone disease are poorly understood. Heparanase, an enzyme that cleaves the heparan sulfate chains of proteoglycans, is upregulated in a variety of human tumors, including myeloma. In the present study, bone marrow biopsies from 40 myeloma patients were stained with antibodies raised against heparanase, RANKL (an osteoclastogenic cytokine), OPG (a decoy receptor for RANKL), TRAP (a marker of osteoclastogenesis) and osteocalcin (a marker of osteoblastogenesis). The radiologic studies for bone lesions of these patients were also recorded. We analyzed the correlations between heparanase expression in bone marrow myeloma cells with (1) the numbers of TRAP positive osteoclasts, (2) RANKL and OPG expression in myeloma cells and osteoblastic cells, (3) the numbers of osteocalcin positive osteoblasts in bone marrow, and (4) the presence/absence of lytic bone lesions. We found a positive correlation between heparanase expression and RANKL expression as well as the numbers of TRAP positive osteoclasts in myeloma and bone marrow cells, but no correlation was found between the expressions of heparanase and OPG in bone marrow cells (myeloma cells do not express OPG). In contrast, heparanase expression was negatively correlated with the numbers of osteocalcin positive osteoblasts. Taken together, these data suggest that heparanase expression by myeloma cells promotes osteoclastogenesis and at same time inhibits osteoblastogenesis. Clinical data show that 92% of patients with high level of heparanase had one or more lytic bone lesions, while only 63% of patients with median∼ low levels of heparanase had bone lesions (p<0.0001). In summary, enhanced heparanase expression in myeloma cells promotes bone resorption and inhibits bone formation; these events contribute to the uncontrolled bone destruction that is characteristic of myeloma. These data provide novel insight into the mechanisms driving myeloma bone disease and suggest that heparanase inhibitors are valid therapeutic targets for the treatment of multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

scholarly journals Comparison of the diagnostic performance and impact on management of 18F-FDG PET/CT and whole-body MRI in multiple myeloma

2021 ◽  
Author(s):  
Olwen Westerland ◽  
◽  
Ashik Amlani ◽  
Christian Kelly-Morland ◽  
Michal Fraczek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Data ◽  
Bone Disease ◽  
Fdg Pet ◽  
Diagnostic Performance ◽  
Whole Body ◽  
Bone Lesions ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Abstract Purpose Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma. Methods Forty-six patients undergoing 18F-FDG PET/CT and WBMRI were reviewed by a nuclear medicine physician and radiologist, respectively, for the presence of myeloma bone disease. Blinded clinical and imaging data were reviewed by two haematologists in consensus and management recorded following clinical data ± 18F-FDG PET/CT or WBMRI. Bone disease was defined using International Myeloma Working Group (IMWG) criteria and a clinical reference standard. Per-patient sensitivity for lesion detection was established. McNemar test compared management based on clinical assessment ± 18F-FDG PET/CT or WBMRI. Results Sensitivity for bone lesions was 69.6% (32/46) for 18F-FDG PET/CT (54.3% (25/46) for PET component alone) and 91.3% (42/46) for WBMRI. 27/46 (58.7%) of cases were concordant. In 19/46 patients (41.3%) WBMRI detected more focal bone lesions than 18F-FDG PET/CT. Based on clinical data alone, 32/46 (69.6%) patients would have been treated. Addition of 18F-FDG PET/CT to clinical data increased this to 40/46 (87.0%) patients (p = 0.02); and WBMRI to clinical data to 43/46 (93.5%) patients (p = 0.002). The difference in treatment decisions was not statistically significant between 18F-FDG PET/CT and WBMRI (p = 0.08). Conclusion Compared to 18F-FDG PET/CT, WBMRI had a higher per patient sensitivity for bone disease. However, treatment decisions were not statistically different and either modality would be appropriate in initial staging, depending on local availability and expertise.

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

scholarly journals International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease

2013 ◽  
Vol 31 (18) ◽  
pp. 2347-2357 ◽  
Author(s):  
Evangelos Terpos ◽  
Gareth Morgan ◽  
Meletios A. Dimopoulos ◽  
Matthew T. Drake ◽  
Suzanne Lentzsch ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Multiple Myeloma ◽  
Spinal Cord Compression ◽  
Bone Disease ◽  
Working Group ◽  
Cord Compression ◽  
Vertebral Compression Fractures ◽  
Bone Lesions ◽  
Published Data ◽  
International Myeloma Working Group

PurposeThe aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) –related bone disease.MethodologyAn interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members.RecommendationsBisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.

What Is Important Factor of Bone Disease in Multiple Myeloma?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4855-4855
Author(s):  
Shoso Munemasa ◽  
Akira Sakai ◽  
Yoshiko Okikawa ◽  
Yoshiaki Kuroda ◽  
Yuta Katayama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cyclin D1 ◽  
Bone Disease ◽  
Tissue Growth ◽  
Good Survival ◽  
Bone Lesions ◽  
Rt Pcr ◽  
Myeloma Cells ◽  
Significant Difference ◽  
Chromosome 13Q

Abstract New International Prognostic Index (IPI) staging system of multiple myeloma (MM) is a combination of the level of serum β2-microglobulin and serum albumin. Particularly, good survival (median survival &gt;5 years) is associated with absence of chromosome 13q deletion. Recently, correlations between molecular subtypes and prognosis have been identified as a good prognosis with t(11;14) and a poor prognosis with t(4;14) and t(14;16) besides chromosome 13 abnormalities. We have reported that some MM cases with cyclin D1 overexpression detected by competitive RT-PCR were not caused by t(11;14)(q13;q32) or extra copies of 11q13 (In J Oncol, in press). A recent report revealed that subtypes of MM cases with the translocation of cyclin D showed a close correlation with bone disease and high level of DKK1. We also have been studing about the correlation between bone disease and bone morphogenetic protein (BMP) 2, or connective tissue growth factor (CTGF) that is supposed to inhibit the VEGF binding to its receptor or modulate cell signaling by BMP. First, we analyzed IPI staging in 91 MM cases, and then analyzed the relation between IPI staging and existence of cyclin D1 overexpression, or t(11;14)(q13;q32) and extra copies of 11q13. Competitive RT-PCR was performed in 77 cases, and cyclin D1 overexpression was detected in 40/77 (52%). Deletion of chromosome 13q was detected in 32/87 (37%), and t(11;14)(q13;q32) or extra copies of 11q13 was detected in 11/50 (22%) and 7/50 (14%), respectively. There were no significant differences of those factors among IPI staging. And we analyzed the scale of bone lesion by bone x-ray in 81 cases. We could not detect the relation between bone disease and cyclin D1 overexpression or translocation of 11q13. Furthermore, we analyzed the expression of BMP2 and CTGF by quantitative real time-PCR in purified myeloma cells or in bone marrow mononuclear cells (BMMNC) reduced myeloma cells less than 5%. We have gotten results that MM cases have a tendency to show higher CTGF expression in BMMNC compared with that of normal BM, but there was no significant difference of BMP2 expression in BMMNC between them. And there was no correlation between cyclin D1 overexpression and BMP2 or CTGF expression. So far a cause of bone lesions in MM is supposed to be the activity of osteoclast, however, our preliminary examination by TRAP staining revealed that osteoclast differentiation from BMMNC in MM cases by adding M-CSF (25 ng/ml) and RANKL (50 ng/ml) decreased compared with that in normal BM, and osteoblast diffentiation also decreased in MM by cytochemical staining for alkaline phosphatase (AP). We guess that both osteoclast and osteobalst differentiation are suppressed in MM and CTGF is a candidate for the suppressor of osteoblast differentiation. We will be able to show the result of AP activity of osteoblast and the effect of recombinant CTGF on osteoblast in meeting.

Serum Concentrations of DKK-1 Correlate with the Extent of Bone Disease in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3518-3518
Author(s):  
Martin Kaiser ◽  
Maren Mieth ◽  
Peter Liebisch ◽  
Susanne Rötzer ◽  
Christian Jakob ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Serum Levels ◽  
Conventional Radiography ◽  
Bone Lesions ◽  
X Rays ◽  
Myeloma Bone Disease ◽  
Lytic Lesions ◽  
Significant Difference ◽  
First Time

Abstract Objectives: Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells was reported to cause inhibition of osteoblast precursors. DKK-1 is an inhibitor of the Wnt/β-catenin signaling, which is a critical signaling pathway for the differentiation of mesenchymal stem cells into osteoblasts. So far there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions. Methods: DKK-1 serum levels were quantified in 184 previously untreated MM patients and 33 MGUS patients by ELISA, using a monoclonal anti-DKK-1 antibody. For the evaluation of bone disease, skeletal X-rays were performed. Results: Serum DKK-1 was elevated in MM as compared to MGUS (mean 11,963 pg/mL versus 1993 pg/mL, P < 0.05). Serum DKK-1 levels significantly correlated with myeloma stage according to Durie and Salmon (mean 2223 pg/mL versus 15,209 pg/mL in stage I and II/III, respectively; P = 0.005). Importantly, myeloma patients without lytic lesions in conventional radiography had significantly lower DKK-1 levels than patients with lytic bone disease (mean 3114 pg/mL versus 17,915 pg/mL; P = 0.003). Of interest, serum DKK-1 correlated with the number of bone lesions (0 vs. 1–3 vs. >3 lesions: mean 3114 pg/mL vs. 3559 pg/mL vs. 24,068 pg/mL; P = 0.002). Conclusion: This is the largest study of DKK-1 serum levels in multiple myeloma patients and data show for the first time a correlation between DKK-1 serum concentration and the amount of lytic bone disease, suggesting that DKK1 is an important factor for the extent of bone disease and supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

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