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Diagnosed with SMM, SPB, or MGUS?

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MGUS, SMM- Cytogenetic Risk, TTP of Multiple Myeloma

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“What determines the risk of progression from asymptomatic to symptomatic myeloma…Most widespread and validated adversely predictive chromosomal aberrations (high-risk aberrations) in this patient cohort consist of…”

Colon polyps, moles, cervical dysplasia, DCIS, Barrett’s esophagus are all forms of pre-cancer, not cancer. These diagnostic terms may increase your risk of cancer. MGUS and SMM are forms of pre-myeloma not multiple myeloma.

A diagnosis of pre-myeloma isn’t really a health problem. This diagnosis may sound scary but you probably feel fine. Many people with MGUS or SMM live for years without developing symptoms, much less developing MM.

The problem is the increased risk of MGUS or SMM becoming frank multiple myeloma (MM).

How do you determine your risk of MM? Diagnostic testing for CRAB, Immunoglobulins, Freelight Chains, your M-spike, the percentage of monoclonal proteins in your bone marrow and finally, probably the most confusing of all diagnostic information, your genetic abnormalities if you have them.

This post focuses exclusively on the issue of genetic abnormalities of a person who has been diagnosed with either MGUS or SMM as a prognostic factor in determining your risk of progression to MM.

According to the studies linked below, the

  • cytogenetic abnormality
  • chromosomal aberrations
  • genetic subentities

listed in the table below are a indicator of risk. One or more genetic abnormalities will increase your risk of MM. A GA will shorten your time to progression (TTP) to MM.

  • Remember that a genetic abnormality is a risk not a certainty
  • Remember that low, intermediate or high risk classification depends on a combination of diagnostic factors
  • Remember that research has identified non-toxic therapies that reduce the risk of multiple myeloma

To learn more about pre-myeloma download the free e-book

David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director of PeopleBeatingCancer

Recommended Reading:


Fluorescence in situ hybridization

Fluorescence in situ hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only those parts of a nucleic acid sequence with a high degree of sequence complementarity.

It was developed by biomedical researchers in the early 1980s[1] to detect and localize the presence or absence of specific DNA sequences on chromosomes. Fluorescence microscopy can be used to find out where the fluorescent probe is bound to the chromosomes.

FISH is often used for finding specific features in DNA for use in genetic counseling, medicine, and species identification.[2] FISH can also be used to detect and localize specific RNA targets (mRNA, lncRNA and miRNA)[citation needed] in cells, circulating tumor cells, and tissue samples. In this context, it can help define the spatial-temporal patterns of gene expression within cells and tissues..”

Advances in the Diagnosis, Classification, Risk Stratification, and Management of Monoclonal Gammopathy of Undetermined Significance: Implications for Recategorizing Disease Entities in the Presence of Evolving Scientific Evidence

“Pathogenesis and Cytogenetic Classification

Race and ethnicity play a role in the pathogenesis of MGUS. African Americans, and blacks from Africa, have a 2- to 3-fold higher incidence of MGUS compared with whites. In contrast, the risk is lower in Asians from Japan and in Mexicans.

Advancing age, male sex, family history, immunosuppression, and exposure to certain pesticides all increase the risk of MGUS.

Understanding the mechanisms that underlie these risk factors will probably provide clues to the etiology of MGUS. The first step in the pathogenesis is likely an abnormal response to antigenic stimulation, mediated possibly by aberrant expression of toll-like receptors and overexpression of interleukin (IL) 6 receptors and IL-1β.

This then results in the development of primary cytogenetic abnormalities, either hyperdiploidy or immunoglobulin heavy chain (IgH) translocations (Table 2).
The progression of MGUS to myeloma is likely secondary to a random second hit, the nature of which is unknown. Ras and p53 mutations, p16 methylation, myc abnormalities, and induction of angiogenesis are all associated with progression…
TABLE 2Cytogenetic Classification of Monoclonal Gammopathy of Undetermined Significance (MGUS)
Cytogenetic abnormality Affected genes
IgH translocated MGUS (50%)
 t(11;14)(ql3;q32) CCND1 (cyclin D1)
 t(4;14)(pl6;q32) FGFR-3 and MMSET
 t(14;16)(q32;q23) C-MAF
 t(6;14)(p21;q32) CCND3 (cyclin D3)
 t(14;20)(q32;q11) MAFB
IgH non-translocated MGUS (50%)
 Hyperdiploid MGUS Numerous

Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load

“What determines the risk of progression from asymptomatic to symptomatic myeloma?…

What about molecular subentities? We know from symptomatic patients that multiple myeloma is a genetically heterogeneous disease.12 Genetic subentities defined by interphase fluorescent in situ hybridization (iFISH) have an impact on a patient’s prognosis under treatment (predictive factors), independent of tumor mass surrogates as defined by the International Staging System (ISS).13,14

Most widespread and validated adversely predictive chromosomal aberrations (high-risk aberrations) in this patient cohort consist of:

  • chromosomal translocation t(4;14),
  • deletion of the short arm of chromosome 17 (del17p),
  • and gain of the long arm of chromosome 1 (+1q21).1517
  • Conversely, hyperdiploidy confers good prognosis.15,18,19

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