Myeloma and Bone Disease

Panaroni, Cristina; Yee, Andrew J.; Raje, Noopur

doi:10.1007/s11914-017-0397-5

Cited by 68 publications

(62 citation statements)

References 192 publications

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“…Multiple myeloma is a malignant hematologic disease of the mature B-cells with a still unfavorable prognosis despite significant advances in treatment [1,2]. It primarily involves the bone marrow where an increasing tumor burden with tumor-associated osteoclast activation and osteoblasts inhibition results in bone destruction called "myeloma bone disease" putting the patients at risk for fracture [3,4]. Bone marrow involvement takes different appearances ranging from diffuse to focal infiltration or a blend of both [5].…”

Section: Introductionmentioning

confidence: 99%

Extended Texture Analysis of Non-Enhanced Whole-Body MRI Image Data for Response Assessment in Multiple Myeloma Patients Undergoing Systemic Therapy

Ekert

Hinterleitner

Baumgärtner

et al. 2020

Cancers

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Identifying MRI-based radiomics features capable to assess response to systemic treatment in multiple myeloma (MM) patients. Retrospective analysis of whole-body MR-image data in 67 consecutive stage III MM patients (40 men; mean age, 60.4 years). Bone marrow involvement was evaluated using a standardized MR-imaging protocol consisting of T1w-, short-tau inversion recovery- (STIR-) and diffusion-weighted-imaging (DWI) sequences. Ninety-two radiomics features were evaluated, both in focally and diffusely involved bone marrow. Volumes of interest (VOI) were used. Response to treatment was classified according to International Myeloma Working Group (IMWG) criteria in complete response (CR), very-good and/or partial response (VGPR + PR), and non-response (stable disease (SD) and progressive disease (PD)). According to the IMWG-criteria, response categories were CR (n = 35), VGPR + PR (n = 19), and non-responders (n = 13). On apparent diffusion coefficient (ADC)-maps, gray-level small size matrix small area emphasis (Gray Level Size Zone (GLSZM) small area emphasis (SAE)) significantly correlated with CR (p < 0.001), whereas GLSZM non-uniformity normalized (NUN) significantly (p < 0.008) with VGPR/PR in focal medullary lesions (FL), whereas in diffuse involvement, 1st order root mean squared significantly (p < 0.001) correlated with CR, whereas for VGPR/PR Log (gray-level run-length matrix (GLRLM) Short Run High Gray Level Emphasis) proved significant (p < 0.003). On T1w, GLRLM NUN significantly (p < 0.002) correlated with CR in FL, whereas gray-level co-occurrence matric (GLCM) informational measure of correlation (Imc1) significantly (p < 0.04) correlated with VGPR/PR. For diffuse myeloma involvement, neighboring gray-tone difference matrix (NGTDM) contrast and 1st order skewness were significantly associated with CR and VGPR/PR (p < 0.001 for both). On STIR-images, CR correlated with gray-level co-occurrence matrix (GLCM) Informational Measure of Correlation (IMC) 1 (p < 0.001) in FL and 1st order mean absolute deviation in diffusely involved bone marrow (p < 0.001). VGPR/PR correlated at best in FL with GSZLM size zone NUN (p < 0.019) and in all other involved medullary areas with GLSZM large area low gray level emphasis (p < 0.001). GLSZM large area low gray level emphasis also significantly correlated with the degree of bone marrow infiltration assessed histologically (p = 0.006). GLCM IMC 1 proved significant throughout T1w/STIR sequences, whereas GLSZM NUN in STIR and ADC. MRI-based texture features proved significant to assess clinical and hematological response (CR, VPGR, and PR) in multiple myeloma patients undergoing systemic treatment.

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Section: Introductionmentioning

confidence: 99%

Extended Texture Analysis of Non-Enhanced Whole-Body MRI Image Data for Response Assessment in Multiple Myeloma Patients Undergoing Systemic Therapy

Ekert

Hinterleitner

Baumgärtner

et al. 2020

Cancers

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“…Osteolytic bone lesions are one of the most common complications of MM, with up to 90% of patients complaining of bone pain. In one third of patients, MM is diagnosed after a bone fracture, leading to severe pain and increased morbidity and mortality [3]. Due to the drugs used for treating MM, many patients suffer from chemotherapy-induced peripheral neuropathy (CIPN), which significantly affects quality of life.…”

Section: Introductionmentioning

confidence: 99%

Pain Management in Patients with Multiple Myeloma: An Update

Coluzzi

Rolke

Mercadante

2019

Cancers

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Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblastic treatments, which have significantly improved overall survival and quality of life. In this review, non-pain specialists will find an overview including a detailed description of physiopathological mechanisms underlying central sensitization and pain chronification in bone pain, the rationale for the correct use of analgesics and invasive techniques in different pain syndromes, and the most recent recommendations published on these topics. The ultimate target of this review was to underlie that different types of pain can be observed in MM patients, and highlight that only after an accurate pain assessment, clinical examination, and pain classification, can pain be safely and effectively addressed by selecting the right analgesic option for the right patient.

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“…Nearly 90% of myeloma patients suffer from skeletal related events during the course of the disease, including severe bone pain, hypercalcemia, pathological fractures and spinal cord compression 3 , that not only affect the quality of life but also the overall survival of MM patients 4 . Myeloma-associated bone disease (MBD) is characterized by an increase in bone-resorptive activity and number of osteoclasts (OCs), as well as impairment of bone-forming activity and differentiation of osteoblasts (OBs), which ultimately lead to the development of osteolytic lesions 5 .…”

Section: Introductionmentioning

confidence: 99%

Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease

García-Gómez

Rodríguez-Ubreva

et al. 2019

Preprint

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and agarciag@carrerasresearch.org Running title: Reverting DNA methylation to treat MM bone disease Abbreviations: mesenchymal stromal cells, osteoblast, multiple myeloma, DNA methylation Abstract word count: 212 Word count: 3999 Figure count: 5 Reference count: 60 ABSTRACT Multiple myeloma (MM) progression and myeloma-associated bone disease (MBD) are highly dependent on the bone marrow (BM) microenvironment, in particular on mesenchymal stromal cells (MSCs). MSCs from MM patients exhibit an abnormal transcriptional profile, suggesting that epigenetic alterations could be governing the tumor-promoting functions of MSCs and their prolonged osteoblast (OB) suppression in MM. In this study, we analyzed the DNA methylome of BM-derived MSCs from patients with monoclonal gammopathy of undetermined significance, smoldering myeloma and symptomatic MM at diagnosis in comparison with their normal counterparts. DNA methylation alterations were found at each of the myeloma stage in association with deregulated expression levels of Homeobox genes involved in osteogenic differentiation. Moreover, these DNA methylation changes were recapitulated in vitro by exposing MSCs from healthy individuals to MM plasma cells. Pharmacological targeting of DNMTs and G9a with the dual inhibitor CM-272, reverted the expression of aberrantly methylated osteogenic regulators and promoted OB differentiation of MSCs from myeloma patients. Most importantly, in a mouse model of bone marrow-disseminated MM, administration of CM-272 prevented tumor-associated bone loss and reduced tumor burden. Our results demonstrated that not only was aberrant DNA methylation a main contributor to bone formation impairment found in MM patients, but also its targeting by CM-272 was able to reverse MM-associated bone loss.

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Myeloma and Bone Disease

Cited by 68 publications

References 192 publications

Extended Texture Analysis of Non-Enhanced Whole-Body MRI Image Data for Response Assessment in Multiple Myeloma Patients Undergoing Systemic Therapy

Extended Texture Analysis of Non-Enhanced Whole-Body MRI Image Data for Response Assessment in Multiple Myeloma Patients Undergoing Systemic Therapy

Pain Management in Patients with Multiple Myeloma: An Update

Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease

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