A Long-Term Study of Prognosis on Monoclonal Gammopathy of Undetermined Significance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4994-4994
Author(s):  
Delvyn Caedren Case ◽  
Marjorie A. Boyd
Keyword(s):  
Bone Marrow ◽  
Disease Progression ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
Bone Lesions ◽  
Monoclonal Protein ◽  
Long Term Study ◽  
Progression Of Disease ◽  
Undetermined Significance

Abstract From 1976 to 2006, 547 patients have been identified and followed for monoclonal gammopathy of undetermined significance (MGUS). Criteria of inclusion included presence of serum monoclonal protein of a concentration of 2 g per deciliter or less; no or moderate amounts of monoclonal light chains in the urine; the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and proportion of plasma cells in the bone marrow of 5% or less. Patients identified as MGUS were followed every 6 months with physical examination, CBC, chemistries, and paraprotein studies. Ages ranged from 32 – 100 years (median 70 years). There were 214 males and 333 females. Over the 30 years of observation, 61 patients have developed disease progression: myeloma 29, lymphoma 12, macroglobulinemia 10, chronic lymphocytic leukemia 7, and amyloid 3. Time to develop myeloma ranged from 2–24 years (median 6 years), macroglobulinemia 2–8 years (median 5 years), and amyloid 3–10 years (median 10 years). Patients developed myeloma throughout the entire period of observation: 2, 3, 3, 4, 4, 4, 4, 5, 5, 5, 6, 6, 6, 6, 6, 7, 7, 8, 8, 9, 10, 10, 11, 14, 15, 15, 18, 20, and 24 years. Survival from diagnosis of myeloma was 1+ – 14+ months (median 36 months) for myeloma and 24 – 108+ months (median 48 months) for macroglobulinemia. The only reliable method of identifying progression of disease to myeloma/macroglobulinemia/amyloid was serial determinations of paraprotein level. In this large series followed for 30 years, with a more restricted diagnosis of MGUS (paraprotein level ≤ 2 g per deciliter and 5% or less bone marrow plasma cells), 1% of all patients identified developed progression of disease. No patient developed disease progression in less than 2 years using the more restricted diagnosis. Risk of progression increased with time with patients developing myeloma even 20 years or longer of follow-up. Serial evaluations of paraprotein levels are indicated in patients identified as MGUS.

scholarly journals Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2107-2111
Author(s):  
JR Berenson ◽  
A Lichtenstein ◽  
S Hart ◽  
D Palomares ◽  
RA Miller
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Similar Frequency ◽  
Murine Monoclonal Antibodies ◽  
Undetermined Significance

Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

scholarly journals Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2107-2111 ◽  
Author(s):  
JR Berenson ◽  
A Lichtenstein ◽  
S Hart ◽  
D Palomares ◽  
RA Miller
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
B Cell Lymphomas ◽  
Similar Frequency ◽  
Murine Monoclonal Antibodies ◽  
Undetermined Significance

Abstract Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

Comparison of Interleukin-1β Expression by In Situ Hybridization in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 300-305 ◽  
Author(s):  
Martha Q. Lacy ◽  
Kathleen A. Donovan ◽  
Julie K. Heimbach ◽  
Gregory J. Ahmann ◽  
John A. Lust
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Interleukin 1Β ◽  
Clinical Feature ◽  
Bone Lesions ◽  
Aberrant Expression ◽  
Undetermined Significance

Abstract We investigated whether interleukin-1β (IL-1β) is differentially expressed in plasma cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients because IL-1β appears to play a major role in the development of lytic bone lesions, the major clinical feature distinguishing MGUS from myeloma. In situ hybridization (ISH) for IL-1β was performed using bone marrow aspirates from 51 MM, 7 smoldering MM, 21 MGUS, and 5 normal control samples. Using the ISH technique IL-1β mRNA was detectable in the plasma cells from 49 of 51 patients with active myeloma and 7 of 7 patients with smoldering myeloma. In contrast, 5 of 21 patients with MGUS and 0 of 5 normal controls had detectable IL-1β message. Bone lesions were present in 40 of the 51 MM patients analyzed, and all 40 patients had IL-1β mRNA by ISH. These results show that greater than 95% of MM patients but less than 25% of MGUS patients are positive for IL-1β production. In the future, continued follow-up of IL-1β positive and negative MGUS patients should determine whether aberrant expression of plasma cell IL-1β is predictive of those MGUS patients that will eventually progress to active myeloma.

scholarly journals Significance of Bone Marrow Plasma Cell Percentage in Patients with Monoclonal Gammopathy of Unknown Significance Developing Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5688-5688
Author(s):  
Mona L Vekaria ◽  
Bharat Rao ◽  
Philip Kuriakose
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Time To Progression ◽  
Bone Marrow Biopsies ◽  
Monoclonal Protein ◽  
Cell Percentage

Abstract Introduction: Monoclonal gammopathies are characterized by the detection of a monoclonal immunoglobulin in the serum or urine and underlying proliferation of a plasma cell/B lymphoid clone. (1) Patients with monoclonal gammopathy of undetermined significance (MGUS) have a clonal plasma cell population in the marrow (<10%) and secrete a monoclonal protein in the serum (<3g/dL) and/or urine. However, they lack clinical features of overt Multiple Myeloma (MM) (lytic bone lesions, anemia, renal impairment and hypercalcemia). In a study from the Mayo Clinic, 59 of 241 patients with MGUS (24%) developed MM over a period of 22 years. (2) The interval from recognition of monoclonal protein to diagnosis of MM ranged from 2-29 years, indicating that patients with MGUS need to be followed indefinitely. Many risk factors have been looked at to identify those with MGUS who are at the highest risk to progress into MM. We hypothesize that a higher number of plasma cells would correlate with a greater risk of progression to MM and sought to find out if this could be documented by arbitrarily dividing patients between < or ≥5% plasma cells seen on initial bone marrow biopsy. Methods: We retrospectively reviewed patients diagnosed with MGUS at Henry Ford Hospital between 1999-2013 who underwent a bone marrow biopsy for documenting plasma cell percentage. In addition to this, we also recorded serum hemoglobin, calcium, creatinine, monoclonal protein type and amount, serum free light chains, beta-2 microglobulin and urine for monoclonal protein at the time of diagnosis of MGUS as well as last completed values. For patients that had skeletal surveys we noted if lytic lesions were present at diagnosis, as well as cytogenetics and karyotype evaluations on bone marrow biopsy samples, if completed. Results: 120 patients with bone marrow biopsies were reviewed. Out of this 17 patients were noted from initial bone marrow biopsy to have ≥10% plasma cells. The remaining 103 patients were categorized as having MGUS. While we were not able to complete full statistical analyses, we did note that 14 of these 103 (13.6%) patients went on to develop overt MM. Further evaluation of these patients revealed that 8 of 14 (57%) had bone marrow biopsies showing ≥5% plasma cells. Interestingly the average time to progression into MM in this subgroup was 1,879 days whereas in the 6 of 14 (43%) with bone marrow biopsy showing <5% plasma cells had average time to progression into MM of 1,965 days. Abnormal cytogenetics and karyotypes of the bone marrow biopsy were also seen in 37.5% of the subgroup of patients with ≥5% plasma cells whereas it was only seen in 16.7% of the subgroup of patients with <5% plasma cells. With statistical data analyses we hope to prove significance in the above collected data as well as make further correlations in regards to risk factors in patients with MGUS. Conclusion: While we have not been able to complete full statistical analyses of the collected data yet, basic review of the above patients with MGUS and ≥5% plasma cells in the bone marrow biopsy showed a trend to develop MM faster by an average of 86 days than those that had <5% plasma cells. These same patients also were more likely to have abnormal cytogenetics and karyotypes of their bone marrow biopsies. There is a need for further investigations to be done in patients with MGUS and higher risk features. It is important that hematologists be able to recognize a high risk MGUS patient as this would lead to closer monitoring and consideration for earlier aggressive treatment to potentially delay progression into overt MM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Follow-up Care of Monoclonal Gammopathy of Undetermined Significance: A Guide for Primary Care Physicians

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Hammad Z ◽  
◽  
Hernandez E ◽  
Tate S ◽  
◽  
...  
Keyword(s):  
Plasma Cell ◽  
Primary Care Physicians ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
M Protein ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
End Organ Damage ◽  
Undetermined Significance

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a condition in which M protein, an abnormal monoclonal immunoglobulin, is present in the blood at a nonmalignant level. Specifically, it is defined by: blood serum M protein concentration <3 g/dL (<30 g/L), <10% plasma cells in the bone marrow, and no evidence of end organ damage [1,2]. Evidence of end organ damage includes hypercalcemia, renal insufficiency, anemia, and bone lesions. These are indicative of MGUS progression and which can be attributed to the monoclonal plasma cell proliferative process [3]. MGUS occurs in 3% of the general population older than 50 years. Incidence increases with age and varies with sex with higher rates observered in males than females [1,4]. MGUS is the most common plasma cell disorder, with 60% of patients that present to the Mayo Clinic with a monoclonal gammopathy being diagnosed with MGUS [3]. While it is typically an asymptomatic condition, it is premalignant disorder to other monoclonal gammopathies. Multiple Myeloma (MM) is almost always preceded by MGUS and the majority of patients will have detectable levels of M protein for at least 5 years prior to MM diagnosis [5,6]. MGUS also precedes immunoglobulin light chain (AL) amyloidosis and Waldenstrom Macroglobulinemia (WM) and tends to progress to disorders at a fixed but unrelenting rate of 1% per year [4].

scholarly journals The role of bone marrow microenvironment in the progression of multiple myeloma from monoclonal gammopathy of undetermined significance

2021 ◽  
Vol 16 (3) ◽  
pp. 26-32
Author(s):  
A. S. Khudovekova ◽  
Ya. A. Rudenko ◽  
A. E. Dorosevich
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Bone Marrow Microenvironment ◽  
Genetic Mutations ◽  
Microbiome Composition ◽  
The Impact ◽  
Undetermined Significance

Multiple myeloma is a tumor of plasma cells, one of the most common malignant blood diseases. It is preceded by a stage called monoclonal gammopathy of undetermined significance, from which true multiple myeloma develops in only a small percentage of cases. It was assumed that this process is associated with the accumulation of genetic mutations, but in recent years there is increasing evidence that the bone marrow microenvironment plays a key role in progression and that it can become a target for therapy that prevents the myeloma development. The review considers the role of mesenchymal stem cells, immune system cells, endotheliocytes, fibroblasts, adipocytes, osteoclasts and osteoblasts in multiple myeloma progression, as well as the impact of the sympathetic nervous system and microbiome composition.

Bone Marrow Biopsy May Be Required During the Initial Evaluation of Individuals with Asymptomatic Monoclonal Gammopathy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5067-5067
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Evangelos Terpos ◽  
Maria Gkotzamanidou ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Incidental Finding ◽  
M Protein ◽  
Monoclonal Protein

Abstract Abstract 5067 The incidental finding of a monoclonal gammopathy during workup for various conditions or in the context of a routine check-up is increasingly common. Several “patients” are then referred for diagnostic evaluation of their monoclonal gammopathy and additional workup is needed. It has been proposed that a bone marrow (BM) aspirate and biopsy is indicated when the monoclonal protein (M-protein) is ≥1.5 g/dL, when abnormalities are noted in the complete blood cell count, serum creatinine level, serum calcium level, or radiographic bone survey, in individuals with non-IgG monoclonal gammopathy and in those with an abnormal serum free light chain (FLC) ratio. The aim of this study was to identify factors that could aid in the evaluation of individuals presenting with asymptomatic monoclonal gammopathy and in whom invasive diagnostic testing with a bone marrow biopsy is considered. Thus, we analyzed our database and identified patients who were referred to the Department of Clinical Therapeutics of the University of Athens, Greece, for evaluation of asymptomatic monoclonal gammopathy and in whom a BM trephine biopsy, a serum and urine protein electrophoresis (SPEP) with immunofixation and quantitative immunoglobulins were performed. SPEPs were scanned and M-protein was measured using imaging analysis software. Patients with a monoclonal M-protein ≥ 3 g/dl (30 g/L), i.e. those diagnosed with asymptomatic/smoldering myeloma (SMM) or Waldenstrom's macorglobulinemia based on the standard criteria, were not included in the analysis. Clonality of BM plasma cells or lymphoplasmacytes was assessed by immunohistochemistry. Patients who eventually were diagnosed with plasma cell related conditions (i.e. amyloidosis, peripheral neuropathy, dermatoses, etc.) were also excluded from the analysis. Our analysis included 161 patients: 53% were females, median age was 64 year (range 33–89 years), 53% had a monoclonal IgG protein, 15.5% had a monoclonal IgA protein, 24% a monoclonal IgM protein and 2.5% had only a monoclonal light chain, while 4% had a biclonal protein. In 64% of patients the monoclonal light chain was kappa and in 37% was lambda. The median serum M-protein was 0.948 g/dl (range 0.1–2.99 g/dl); 52% of patients had an M-protein of <1 g/dl and 79% of <2 g/dl. Immunoparesis of at least one of the uninvolved immunoglobulins was present in 38% of cases and of both of the uninvolved immunoglobulins in 6%. Median BM infiltration by monoclonal plasma cells or lymphoplasmacytes was 15%. In 66.5% of individuals there was a BM infiltration of ≥10% by monoclonal plasma cells or lymphoplasmacytes, while in 10% of the studied cases the BM infiltration was ≥50%. A significant correlation of the size of M-protein and of the infiltration of the BM was found (R=0.592, p<0.001). However, 27% of patients with M-protein <0.5 g/dl had ≥10% clonal plasma cells or lymphoplasmacytes in their BM biopsies. The respective rates were 46% for those with M-protein <1 g/dl, 54% for those with M-protein 1.5 g/dl and 58% for those with M-protein <2 g/dl. Ninety per cent of those who had immunoparesis of at least one of the uninvolved immunoglobulins had ≥10% clonal plasma cells or lymphoplasmacytes. A BM infiltration of ≥10% was more frequent in individuals with a monoclonal IgG or IgA protein (72% and 80%, respectively) vs. 45% of those with a monoclonal IgM protein (p=0.015). Light chain isotype, age and gender were not predictive of the degree of BM plasma cell infiltration. In multivariate analysis, immunoparesis of at least one of the uninvolved immunoglobulins (OR: 6.45, 95% CI: 2.32–18, p<0.001), an IgG or IgA monoclonal protein (OR: 2.67, 95% CI: 1.1–6.4, p=0.028) and an M-protein of ≥1 g/dl (OR: 5.4, 95% CI: 2.23–13) were independently associated with the presence of ≥10% of clonal infiltration in BM biopsy. By combining the above risk factors we found that in those who had all three, 97% had ≥10% clonal cells in the BM biopsy, while in those with 0–1 of the above factors the probability to find ≥10% clonal cells was 43%. These findings indicate that even patients with low risk for BM infiltration by clonal plasma cells, may be diagnosed as SMM when a BM biopsy is performed. In conclusion, our data on a large number of individuals with asymptomatic monoclonal gammopathy who underwent a BM biopsy may indicate that the latter exam may provide useful information and could be included in the standard initial workup of these individuals. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3650
Author(s):  
Vanessa Desantis ◽  
Antonio Giovanni Solimando ◽  
Ilaria Saltarella ◽  
Antonio Sacco ◽  
Viviana Giustini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Hematological Malignancy ◽  
Bone Lesions ◽  
Step Process ◽  
Asymptomatic Phase ◽  
Undetermined Significance ◽  
Premalignant Conditions

Multiple myeloma (MM) is a hematological malignancy characterised by proliferation of clonal plasma cells (PCs) within the bone marrow (BM). Myelomagenesis is a multi-step process which goes from an asymptomatic phase, defined as monoclonal gammopathy of undetermined significance (MGUS), to a smouldering myeloma (SMM) stage, to a final active MM disease, characterised by hypercalcemia, renal failure, bone lesions anemia, and higher risk of infections. Overall, microRNAs (miRNAs) have shown to significantly impact on MM tumorigenesis, as a result of miRNA-dependent modulation of genes involved in pathways known to be crucial for MM pathogenesis and disease progression. We aim to revise the literature related to the role of miRNAs as potential diagnostic and prognostic biomarkers, thus highlighting their key role as novel players within the field of MM and related premalignant conditions.

scholarly journals Characterization of Monoclonal Gammopathy of Undetermined Significance Progression to Multiple Myeloma through Meta-Analysis of GEO Data

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4395-4395
Author(s):  
Jihad Aljabban ◽  
David Chen ◽  
Francesca Cottini ◽  
Saad Syed ◽  
Nabeal Aljabban ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Signaling Pathways ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Upstream Regulators ◽  
Undetermined Significance

Background: Monoclonal gammopathy of undetermined significance (MGUS) is characterized by plasma cell production of abnormal monoclonal protein, or M protein. While MGUS itself is asymptomatic, it generally carries a 1% per year risk to progression to multiple myeloma (MM). The etiology of MGUS, as well as why it progresses to MM in some cases, remains unclear. Moreover, it is not known why some MGUS patients, such as African Americans, have higher risk to progression to MM. Contrasting MGUS and MM can potentially highlight genes that differentiate benign gammopathies from malignant ones and may be involved in disease progression from MGUS to MM. Methods: We employed our STARGEO platform to tag samples from the NCBI Gene Expression Omnibus and performed two separate meta-analysis to compare MGUS and MM transcriptomes. For the first meta-analysis, we tagged MGUS plasma cells recovered from the bone marrow of 101 patients and tagged plasma cells from 64 healthy subjects as a control. For the second analysis. We tagged CD138+ cells from the bone marrow of 383 MM patients and used the MGUS tagged samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis (IPA). Results: From our first meta-analysis of MGUS, we identified EIF2 signaling, regulation of EIF4 and p70S6K signaling, and JAK/STAT signaling as top canonical pathways. Top upstream regulators included TP53, TGFB1, and the proto-oncogene MYCN and MYC (with predicted activation). The most upregulated genes included pro-oncogenes such as KIT and MLLT3, which is well-studied in acute leukemia but not yet described in MGUS. Another top upregulated gene was NRG3, a myeloma growth factor. Additionally, our analysis highlighted key genes involved in transcription and epigenetic regulation. For example, there was upregulation of RBFOX2, which is involved in alternative splicing during oncogenesis and tumor progression, and of PARP15, a transcriptional repressor with poly(ADP-ribose) polymerase activity and candidate gene for drug targeting. Also, there was upregulation of the DNA damage-inducible gene GADD45A, found to promote global DNA methylation. Lastly, we found upregulation of COMMD3, a gene with a recently identified role in humoral activity and B cell migration. From our second meta-analysis comparing MM and MGUS directly, we identified mitochondrial dysfunction, oxidative phosphorylation, purine nucleotides de novo biosynthesis, and sirtuin signaling as top upstream regulators. Like our first analysis, TP53 (with predicted inhibition), TGFB1, and MYC (with predicted activation) were top upstream regulators. The most upregulated gene was NUP62, a nucleoporin and novel regulator of cell proliferation and inducer of MYC activity. Our analysis also illustrated pro-oncogenic signaling pathways such as the Wnt pathway through upregulation of the ubiquitin ligase RNF14 and serine/threonine kinase through upregulation of SRPK2. Moreover, we found upregulation of the super-enhancer DUSP4, a phosphatase whose over-activity may drive MM severity. Lastly, we found upregulation of lysosomal associated membrane protein LAMP5. LAMP5 was recently identified in single-cell RNA sequencing of MM patients and may play a significant role in disease. Conclusions: Our study illustrates signaling pathways in MGUS that are present in MM such as EIF2, JAK/STAT, and MYC signaling. We also illustrate gene activity in MGUS that may predispose to MM progression such as NRG3, RBFOX2, and PARP15. GADD45RA and COMMD3 may play novel roles in MGUS. Our second analysis highlighted disease activity that persist from MGUS to MM, such as MYC signaling. It is possible that the genes from this analysis that aims to distinguish MM from MGUS may be responsible for tipping the scales from benignity to malignancy. Genes such as DUSP4, RN14, LAMP5, and others could serve as novel biomarkers or targets to MM and risk of progression of MGUS to MM. Disclosures No relevant conflicts of interest to declare.

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