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Blood Cancer J 2022 04 19;12(4):67. Epub 2022 Apr 19.

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal disorder that progresses to multiple myeloma (MM), or other plasma-cell or lymphoid disorders at a rate of 1%/year. We evaluate the contribution of body mass index (BMI) to MGUS progression beyond established clinical factors in a population-based study. We identified 594 MGUS through a population-based screening study in Olmsted County, Minnesota, between 1995 and 2003. Read More

Am Soc Clin Oncol Educ Book 2022 Apr;42:1-10

Department of Hematology, Cebeci Hospital, Ankara University Dikimevi, Ankara, Turkey.

Our knowledge of monoclonal gammopathies is continuously evolving. Once accepted as a possible precursor condition to multiple myeloma, monoclonal gammopathies as an entity are now associated with many renal, neurologic, and dermatologic disorders of clinical significance. This change has created a challenge for patients and clinicians, as a monoclonal gammopathy may be a harbinger not of multiple myeloma but of other lymphoproliferative disorders such as light-chain amyloidosis and Waldenström macroglobulinemia. Read More

SAGE Open Med Case Rep 2022 22;10:2050313X221086321. Epub 2022 Mar 22.

Division of Dermatology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.

Background: Hypergammaglobulinemic purpura of Waldenström is an uncommon disease, which presents mostly in women on the lower extremities. It is sometimes associated with underlying immune dysregulation. Sjögren syndrome is the most common association; however, rare occurrences of the self-resolving syndrome with lymphoma or myeloma have been reported. Read More

J Investig Med High Impact Case Rep 2022 Jan-Dec;10:23247096211052187

Louisiana State University Health Sciences Center New Orleans, USA.

A patient was diagnosed with Waldenström's macroglobulinemia (WM) after the initial findings of anemia and ophthalmological findings of retinal hemorrhage. Upon further workup, the patient was found to have an IgM predominant monoclonal gammopathy on serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP). This highlights the need for open communication between different specialties, streamlining rapid and accurate diagnosis. Read More

Hematology Am Soc Hematol Educ Program 2021 12;2021(1):662-672

Myeloma Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.

In the 1960s, Dr Jan Waldenström argued that patients who had monoclonal proteins without any symptoms or evidence of end-organ damage represented a benign monoclonal gammopathy. In 1978, Dr Robert Kyle introduced the concept of "monoclonal gammopathy of undetermined significance" (MGUS) given that, at diagnosis, it was not possible with available methods (ie, serum protein electrophoresis to define the concentration of M-proteins and microscopy to determine the plasma cell percentage in bone marrow aspirates) to determine which patients would ultimately progress to multiple myeloma. The application of low-input whole-genome sequencing (WGS) technology has circumvented previous problems related to volume of clonal plasma cells and contamination by normal plasma cells and allowed for the interrogation of the WGS landscape of MGUS. Read More

Thromb Res 2022 01 22;209:1-4. Epub 2021 Nov 22.

Hemostasis Laboratory, Grenoble Alpes University Hospital Grenoble, France; Univ. Grenoble Alpes, Faculty of Medicine, Grenoble, France. Electronic address:

Blood Adv 2022 01;6(1):189-199

Department of Clinical Therapeutics, School of Medicine.

We describe a novel method for the detection of MYD88L265P mutation using a competitive allele-specific polymerase chain reaction (Cast-PCR) assay. This assay has a sensitivity of 1 × 10-3, is applicable in reactions containing very low amounts of DNA (as low as 20 pg), and allowed the detection of MYD88L265P somatic mutation in both tumor-derived DNA (tDNA) and cell-free DNA (cfDNA). In addition, using the Cast-PCR assay, we were able to determine the mutation allele fraction (MAF) in each tested sample. Read More

Dermatol Online J 2021 Aug 15;27(8). Epub 2021 Aug 15.

Department of Dermatology, Venereology and Allergology, University Medical Center, Göttingen.

Eosinophilic fasciitis (EF) and generalized morphea (GM) are rare and difficult-to-treat sclerosing skin diseases which may occur in association with hematologic disorders. We present a 66-year-old man with EF and associated Waldenström macroglobulinemia who received combination therapy with rituximab (375mg/m2 every other week, gradually extended to every eight weeks), prednisolone (1.25-30mg/d), and methotrexate (7. Read More

Orv Hetil 2021 09 19;162(38):1533-1540. Epub 2021 Sep 19.

1 Semmelweis Egyetem, Általános Orvostudományi Kar, Szemészeti Klinika, Budapest, Mária u. 39., 1085.

Összefoglaló. Célkitűzés: A monoklonális gammopathia szemészeti jeleinek és szövődményeinek vizsgálata. Betegek és módszerek: Két nagy budapesti hematológiai ellátóhely 1999 és 2020 között diagnosztizált és/vagy kezelt, monoklonális gammopathiát mutató betegeit vizsgáltuk (42 beteg 84 szeme, 42,86% férfi; átlagéletkor 63,83 ± 10,76 év). Read More

Int J Clin Pract 2021 Nov 21;75(11):e14817. Epub 2021 Sep 21.

Department of Internal Medicine, Centre de référence des maladies auto-inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA), Sorbonne University, AP-HP, Tenon Hospital, Paris, France.

Introduction: AL amyloidosis is caused by the proliferation of an immunoglobulin-secreting B cell clone. AA amyloidosis is a rare complication of chronic inflammation. However, some patients present with diseases combining monoclonal immunoglobulin production and chronic inflammation. Read More

Blood Cells Mol Dis 2021 11 14;91:102595. Epub 2021 Jul 14.

Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, USA; Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Clin Geriatr Med 2021 05;37(2):301-312

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

This article provides an overview of the clinical features, diagnosis, and treatment of the major paraprotein-related peripheral neuropathies, including monoclonal gammopathy of undetermined significance, Waldenström macroglobulinemia, POEMS syndrome, multiple myeloma, transthyretin amyloidosis, and light chain amyloidosis. For each paraprotein neuropathy, the epidemiology, demographics, systemic findings, and electrophysiologic features are presented. Pharmacologic treatment of transthyretin amyloid polyneuropathy also is reviewed. Read More

Cancer 2021 06 25;127(12):2039-2048. Epub 2021 Mar 25.

Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Waldenström macroglobulinemia (WM) is a rare chronic B-cell lymphoma. Familial clustering of WM has been observed over the years. However, little is known about the contribution of inherited genetic variants to familial WM cases. Read More

Am J Hematol 2021 07 25;96(7):846-853. Epub 2021 Mar 25.

Mayo Clinic, Rochester, Minnesota, USA.

Despite the benign nature of monoclonal gammopathy of undetermined significance (MGUS), mounting data are associating MGUS with the development of organ dysfunction, specifically monoclonal gammopathy of renal significance (MGRS) and monoclonal gammopathy of neurological significance (MGNS), which could be associated with substantial morbidity. Emerging evidence suggests that patients with MGRS and MGNS could benefit from treatments used for myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia, depending on the underlying pathology. However, the treatment of MGRS and MGNS is not standardized, and potentially effective therapies might not be reimbursed because these conditions do not formally meet the criteria for malignant processes. Read More

Redox Biol 2021 05 4;41:101927. Epub 2021 Mar 4.

Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

The molecular events that modulate the progression of monoclonal gammopathy of undetermined significance of the immunoglobulin M class (IgM-MGUS) to Waldenstrom Macroglobulinemia (WM) are mostly unknown. We implemented comparative proteomics and metabolomics analyses on patient serum samples to identify differentially expressed molecules crucial to the progression from IgM-MGUS to WM. Our data identified altered lipid metabolism as a discriminating factor between MGUS, WM, and matched normal controls. Read More

Neurology 2021 02 4;96(5):214-225. Epub 2020 Dec 4.

From the Department of Neurology (J.-M.V., M.D., L.R., K.G., L.M.), National Reference Center for "Rare Peripheral Neuropathies," Dupuytren University Hospital (CHU Limoges), University of Limoges; Department of Pathology (M.D.), Limoges University Hospital (CHU Limoges), University of Limoges; Department of Neurology and ALS Reference Center (P.C.), Bretonneau University Hospital (CHU Tours), University of Tours; and Department of Neurology (S.M.), Nerve-Muscle Unit, 4 Pellegrin University Hospital (CHU Bordeaux), University of Bordeaux, France.

Monoclonal gammopathy is encountered quite frequently in the general population. This type of hematologic abnormality may be mild, referred to as monoclonal gammopathy of undetermined significance or related to different types of hematologic malignancies. The association of a peripheral neuropathy with monoclonal gammopathy is also fairly common, and hemopathy may be discovered in an investigation of peripheral neuropathy. Read More

Ann Biol Clin (Paris) 2020 10;78(5):527-536

Service d'hématologie biologique, Hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, Paris, France.

We report the case of a man with a primary diagnosis of Waldenström macroglobulinemia. He secondarily presented a diffuse large B cell lymphoma (DLBCL) located in the nasal fossae, which relapsed later in the eye. The diagnosis of these two malignancies is based on a multidisciplinary biological approach using new sensitive and specific techniques. Read More

Br J Haematol 2021 03 11;192(5):843-852. Epub 2020 Aug 11.

Haematology Department, University Hospital of Salamanca, Research Biomedical Institute of Salamanca (IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), Salamanca, Spain.

Deletion of the long arm of chromosome 6 (del6q) is the most frequent cytogenetic abnormality in Waldenström macroglobulinaemia (WM), occurring in approximately 50% of patients. Its effect on patient outcome has not been completely established. We used fluorescence in situ hybridisation to analyse the prevalence of del6q in selected CD19+ bone marrow cells of 225 patients with newly diagnosed immunoglobulin M (IgM) monoclonal gammopathies. Read More

Neoplasma 2020 Jul 23;67(4):939-945. Epub 2020 Jun 23.

Department of Internal Medicine, Hematology and Oncology, University Hospital, Masaryk University, Brno, Czech Republic.

Monoclonal gammopathy of undetermined significance (MGUS) is a known precursor of more serious cancers, such as multiple myeloma (MM), Waldenström macroglobulinemia (MW) and other lymphoproliferative disorders. Using 18F-FDG PET/CT, we aimed to evaluate its benefit in early detection of various accompanying disorders and illnesses in MGUS patients. We prospectively analyzed the diagnostic relevance of 18F-FDG PET/CT in 390 newly diagnosed MGUS patients. Read More

Ugeskr Laeger 2020 03;182(10)

This review summarises the work-up of patients with monoclonal gammopathy of undetermined significance (MGUS). In persons above 70 years of age, around 5% have MGUS, a premalignant state with a monoclonal plasma immunoglobulin or light chain (M protein) in blood and/or urine. Continuous follow-up is recommended due to a risk of malignant progression of around 1% per year. Read More

J Clin Pathol 2020 Sep 24;73(9):571-577. Epub 2020 Jan 24.

Anatomic Pathology Service, Hematology Service and Translational Hematopathology Lab, Hospital Universitario Marques de Valdecilla/IDIVAL. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Santander, Cantabria, Spain

Aims: The aim of this study was to describe the characteristics of the bone marrow infiltration found in a series of clinically defined lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinaemia (WM) and IgM-monoclonal gammopathy of undetermined significance (MGUS) and to perform a targeted next-generation sequencing (NGS) for the identification of additional somatic mutations to p.L265P in LPL/WM.

Methods: We have reviewed a series of 35 bone marrow biopsies from 28 patients with a clinical diagnosis of LPL/WM (24 cases) or MGUS (4 cases). Read More

Hematol Oncol 2020 Feb 18;38(1):111-113. Epub 2019 Dec 18.

ASST Grande Ospedale Metropolitano Niguarda, Department of Hematology, Niguarda Cancer Center, Milan, Italy.

PLoS One 2019 4;14(9):e0221941. Epub 2019 Sep 4.

Department of Hematology, Chiba University Hospital, Chiba, Japan.

We investigated the feasibility of using next-generation sequencing (NGS) technique using molecular barcoding technology to detect MYD88 L265P mutation in unselected peripheral blood mononuclear cells (PBMCs) in 52 patients with Waldenström's macroglobulinemia [1] and 21 patients with IgM-monoclonal gammopathy of undetermined significance (MGUS). The NGS technique successfully detected the MYD88 L265P in unselected PBMCs at a sensitivity of 0.02%, which was ×5 higher than that of AS-PCR. Read More

Curr Opin Neurol 2019 10;32(5):658-665

National Hospital for Neurology and Neurosurgery, Centre for Neuromuscular Disease, Queen Square, London, England.

Purpose Of Review: There is an increasingly recognized association between haematological and neurological disease. This is especially true in the peripheral nervous system in which, to an extent, proof of a link is easier to achieve. The most sensitive low level paraprotein detection methods should always be employed in which a paraprotein is suspected. Read More

Br J Haematol 2019 11 12;187(4):413-415. Epub 2019 Jul 12.

Division of Haematology, Mayo Clinic, Rochester, MN, USA.

Br J Haematol 2019 11 5;187(4):441-446. Epub 2019 Jul 5.

Division of Haematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenström macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1-2% per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow-up of 83 months (1214 person-years), 15 patients (8·5%) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). Read More

Rev Prat 2018 Sep;68(7):777-784

CHU de Rennes, service de médecine interne, hôpital Sud, Rennes, France. Faculté de médecine de Rennes, université Rennes-1, Rennes, France.

Conduct in case of monoclonal gammapathy ? Monoclonal gammopathies are frequent in general population (about 3 % beyond 50 years) and their prevalence increases with age. They may be associated with malignant haemopathy (multiple myeloma for IgG and IgA, Waldenström disease for IgM). In absence of malignant haemopathy, the diagnosis is that of monoclonal gammopathy of indeterminate significance (MGUS). Read More

Ann Rheum Dis 2019 05 12;78(5):583-585. Epub 2019 Jan 12.

Department of Clinical Sciences Lund, Rheumatology, Medical Faculty, Lund University, Lund 22185, Sweden

Klin Onkol Summer 2018;31(4):270-276

Background: Monoclonal gammopathy of undetermined significance (MGUS) is one of the most prevalent premalignant conditions associated with a risk of malignant transformation to multiple myeloma (MM) or other forms of lymphoproliferative disorders with risk of progression of approximately 1% per year. IgG and IgA MGUS are precursor conditions of multiple myeloma (MM), whereas light-chain MGUS is a precursor condition of light chain MM. IgM MGUS is a precursor condition of Waldenström macroglobulinemia (MW) or other lymphoproliferative diseases. Read More