Comparison of intramedullary myeloma and corresponding extramedullary soft tissue plasmacytomas using genetic mutational panel analyses

Haart, Sanne J. de; Willems, Stefan M.; Mutis, Tuna; Koudijs, Marco J.; Blokland, M T van; Lokhorst, Henk M.; Weger, Roel A. de; Minnema, Monique C.

doi:10.1038/bcj.2016.35

Cited by 26 publications

(27 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For this reason, suitable PB markers of molecular relapse allowing earlier initiation of treatment are needed. cfDNA is released from multiple independent tumor sites representing the entire tumor genome and seems to be the ideal molecule for further studies.…”

Section: Lymphoid Malignanciesmentioning

confidence: 99%

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Kubaczková

Vrábel

Sedlaříková

et al. 2017

European J of Haematology

View full text Add to dashboard Cite

Although tumor cells are the most reliable source of tumor DNA, biopsy of the tumor is an invasive procedure that should be avoided in some cases. The main limitation of any biopsy is sampling of one tumor site, which may not represent all malignant clones due to the heterogeneity of the tumor. These clones respond to treatment differently and thus directly influence survival of the patient. Circulating cell-free DNA (cfDNA) is released from multiple tumor sites, reflects overall heterogeneity of the tumor, and correlates with its progression. Detection of tumor-specific genetic and epigenetic aberrations in cfDNA could have a direct impact on molecular diagnosis, prognosis, follow-up of disease, monitoring of minimal residual disease, and response to treatment. While most cfDNA data are still experimental, they are very promising. This review focuses on cfDNA in hematological malignancies. K E Y W O R D Sacute lymphoblastic leukemia, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes | INTRODUCTION AND HISTORYIn recent years, significant advances in diagnosis and treatment of cancer have been made. Nevertheless, invasive and painful procedures, such as tissue or bone marrow (BM) biopsy, are gold standard for disease diagnosis and monitoring. At the same time, they should be avoided in some cases-if BM is fibrotic or tumor tissue is not easily accessible.1 As a single tumor site is sampled during BM biopsy, it may not contain all malignant clones. 2,3 As these clones react to treatment differently, they directly influence survival of patients; thus, easily accessible markers that would mirror the entire heterogeneity of the tumor are sought after. Such putative markers are present in peripheral blood (PB), for example, circulating tumor cells (CTC) or circulating nucleic acids. 3,4 Biopsies of PB-the so-called liquid biopsies-are at the center of attention of researchers as well as clinicians and represent a newer and more comprehensive approach to obtain tumor information. Analysis of circulating molecules (microRNA, cell-free DNA, and others) as well as CTC might describe the tumor in more detail.Cell-free DNA (cfDNA) is one of these possibilities.CfDNA is formed by DNA fragments. These fragments are gathered from all tumor sites into circulation; thus, they mirror the complexity and heterogeneity of the entire tumor. 3 CfDNA may serve as an excellent diagnostic marker as it reflects the disease in more detail than existing biomarkers. Moreover, because of easy access, cfDNA sampling is suitable for repeated analyses. 4 As it correlates with disease progression, it could serve as a prognostic marker as well. 5,6The first reference of cfDNA dates back to 1948. In that year, CfDNA may shortly become such a marker. | CHARACTERISTICS OF CFDNAMolecules of cfDNA are extracellular fragments of short doublestranded DNA found in PB and other body fluids, for example, in urine, saliva, breast milk, and synovial fluid. 16,17 Generally, cfDNA is found in very low concentrations in PB of HD (10-100...

show abstract

Section: Lymphoid Malignanciesmentioning

confidence: 99%

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Kubaczková

Vrábel

Sedlaříková

et al. 2017

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…The terminal stage of myeloma progression is characterized by stromaindependent growth, which results in extramedullary diseases and plasma cell leukemia. Genetic abnormalities associated with this stage include mutational inactivation of TP53 [13], the protocadherin family [14], and inhibitory components of the NF-κB pathway [15]. In addition, NGS analyses uncovered non-synonymous point mutations of epigenetic regulators such as KDM6A/UTX (10 %), KDM6B/JMJD3, MMSET (8 %), MLL (1 %) and HOXA9 [6,10].…”

Section: Mechanisms Of Action Of Novel Drugs In Multiple Myeloma and mentioning

confidence: 99%

Epigenetic mechanisms of cell adhesion-mediated drug resistance in multiple myeloma

Furukawa

Kikuchi

2016

Int J Hematol

View full text Add to dashboard Cite

Multiple myeloma cells acquire the resistance to anti-cancer drugs through physical and functional interactions with the bone marrow microenvironment via two overlapping mechanisms. First, bone marrow stromal cells (BMSCs) produce soluble factors, such as interleukin-6 and insulin-like growth factor-1, to activate signal transduction pathways leading to drug resistance (soluble factor-mediated drug resistance). Second, BMSCs up-regulate the expression of cell cycle inhibitors, anti-apoptotic members of the Bcl-2 family and ABC drug transporters in myeloma cells upon direct adhesion [cell adhesion-mediated drug resistance (CAM-DR)]. Elucidation of the mechanisms underlying drug resistance may greatly contribute to the advancement of cancer therapies. Recent investigations, including ours, have revealed the involvement of epigenetic alterations in drug resistance especially CAM-DR. For example, we found that class I histone deacetylases (HDACs) determine the sensitivity of proteasome inhibitors and the histone methyltransferase EZH2 regulates the transcription of anti-apoptotic genes during the acquisition of CAM-DR by myeloma cells. In addition, another histone methyltransferase MMSET was shown to confer drug resistance to myeloma cells by facilitating DNA repair. These findings provide a rationale for the inclusion of epigenetic drugs, such as HDAC inhibitors and histone methylation modifiers, in combination chemotherapy for MM patients to increase the therapeutic index.

show abstract

“…Notably, one patient harboured both KRAS and NRAS mutations highlighting that diversification and heterogeneity in this pathway may exist before the development of symptomatic MM [17]. To date the mutational characterisation of MM has utilised single-site BM biopsies, however, it is now increasingly recognised that such an approach may fail to capture the spatial and temporal genetic heterogeneity of this multi-focal disease, self-evidently with EM MM, but also, based on emerging data, in patients with 'typical MM' manifesting intra-clonal heterogeneity [11,[18][19][20]. Moreover, both spatial and temporal genetic heterogeneity are now recognised as adding to the genetic complexity of the disease as it evolves [21].…”

Section: Multiple Myelomamentioning

confidence: 99%

Liquid Biopsy in Multiple Myeloma

Mithraprabhu¹,

Spencer²

2018

Hematology - Latest Research and Clinical Advances

View full text Add to dashboard Cite

Liquid biopsies represent an innovative methodology for cancer diagnostics and disease monitoring. The analysis of circulating cell-free nucleic acids (CFNA) and circulating tumour cells (CTC) are rapidly being adopted for quantitative and qualitative characterisation of the tumour genome and as a mode of non-invasive therapeutic monitoring. Circulating cell-free DNA (cfDNA) and CTC are representative of the underlying mutational profile of a cancer whereas the evaluation of extracellular RNA (exRNA) can be utilised as a prognostic biomarker thus providing critical biological information both at the time of diagnosis and during disease evolution. In this chapter, we will review the emerging utility of CFNA and CTC as biomarkers of prognosis and for both mutational characterisation and monitoring disease progression, and how these have the potential to provide additional information as an adjunct to bone marrow biopsies and conventional disease markers in multiple myeloma (MM). Emerging data suggest that liquid biopsies might offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognostication and therapeutic decision making in MM, with particular applicability in subsets of patients where conventional markers of disease burden may be less informative.

show abstract

Comparison of intramedullary myeloma and corresponding extramedullary soft tissue plasmacytomas using genetic mutational panel analyses

Cited by 26 publications

References 15 publications

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Epigenetic mechanisms of cell adhesion-mediated drug resistance in multiple myeloma

Liquid Biopsy in Multiple Myeloma

Contact Info

Product

Resources

About