Molecular Pathogenesis of Multiple Myeloma: Clinical Implications
Francesco Maura1, Peter Leif Bergsagel2
1University of Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA.
Hematology/Oncology Clinics of North America
|January 10, 2024
Summary
Multiple myeloma, a plasma cell cancer, develops from monoclonal gammopathy. Genetic changes like translocations and mutations drive its progression from a stable precursor condition to malignant disease.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Multiple myeloma is a cancer of plasma cells in the bone marrow.
- It is often preceded by monoclonal gammopathy, a less severe condition.
- Both conditions share specific genetic alterations.
Purpose of the Study:
- To outline the genetic underpinnings of multiple myeloma and its precursor.
- To identify key genetic events in disease progression.
Main Methods:
- Review of genetic alterations in multiple myeloma and monoclonal gammopathy.
- Analysis of gene translocations and mutations associated with disease progression.
Main Results:
- Common genetic features include immunoglobulin heavy gene translocations affecting cyclin D genes (CCND1, CCND2, CCND3) or maf family genes (MAF, MAFB, MAFA), or NSD2/FGFR3 alterations.
- Hyperdiploidy is also observed in both conditions.
- Progression to malignancy involves tumor suppressor gene inactivation and mutations in MYC, RAS, NFkB, and cell cycle pathways.
Conclusions:
- Multiple myeloma pathogenesis involves specific genetic translocations and mutations.
- These genetic events dysregulate cell cycle and signaling pathways, leading to malignant transformation.
Keywords:
HyperdiploidyMYCMonoclonal gammopathy of undetermined significance (MGUS)Multiple myeloma (MM)NFkBPlasma cell (PC)RASSmoldering multiple myeloma (SMM)More Related Videos
10:04Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
Published on: May 1, 2015
13.1K
09:41An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
8.7K
Related Concept Videos
01:15Differentiation of Common Myeloid Progenitor Cells
3.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K
02:07Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
02:30Metastasis
5.5K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.5K
02:57Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K