Genome Instability in Multiple Myeloma: Facts and Factors
Multiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/23/5949 |
| _version_ | 1797507966004363264 |
|---|---|
| author | Anna Y. Aksenova Anna S. Zhuk Artem G. Lada Irina V. Zotova Elena I. Stepchenkova Ivan I. Kostroma Sergey V. Gritsaev Youri I. Pavlov |
| author_facet | Anna Y. Aksenova Anna S. Zhuk Artem G. Lada Irina V. Zotova Elena I. Stepchenkova Ivan I. Kostroma Sergey V. Gritsaev Youri I. Pavlov |
| author_sort | Anna Y. Aksenova |
| collection | DOAJ |
| description | Multiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability to patients. Despite current progress in MM treatment, the disease invariably recurs, even after the transplantation of autologous hematopoietic stem cells (ASCT). Biological processes leading to a pathological myeloma clone and the mechanisms of further evolution of the disease are far from complete understanding. Genetically, MM is a complex disease that demonstrates a high level of heterogeneity. Myeloma genomes carry numerous genetic changes, including structural genome variations and chromosomal gains and losses, and these changes occur in combinations with point mutations affecting various cellular pathways, including genome maintenance. MM genome instability in its extreme is manifested in mutation <i>kataegis</i> and complex genomic rearrangements: chromothripsis, templated insertions, and chromoplexy. Chemotherapeutic agents used to treat MM add another level of complexity because many of them exacerbate genome instability. Genome abnormalities are driver events and deciphering their mechanisms will help understand the causes of MM and play a pivotal role in developing new therapies. |
| first_indexed | 2024-03-10T04:55:55Z |
| format | Article |
| id | doaj.art-14e44f83d1f047bbbfe856dfa25da4cb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:55:55Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-14e44f83d1f047bbbfe856dfa25da4cb2023-11-23T02:11:59ZengMDPI AGCancers2072-66942021-11-011323594910.3390/cancers13235949Genome Instability in Multiple Myeloma: Facts and FactorsAnna Y. Aksenova0Anna S. Zhuk1Artem G. Lada2Irina V. Zotova3Elena I. Stepchenkova4Ivan I. Kostroma5Sergey V. Gritsaev6Youri I. Pavlov7Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, RussiaInternational Laboratory “Computer Technologies”, ITMO University, 197101 St. Petersburg, RussiaDepartment of Microbiology and Molecular Genetics, University of California, Davis, CA 95616, USADepartment of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, RussiaRussian Research Institute of Hematology and Transfusiology, 191024 St. Petersburg, RussiaRussian Research Institute of Hematology and Transfusiology, 191024 St. Petersburg, RussiaEppley Institute for Research in Cancer, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USAMultiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability to patients. Despite current progress in MM treatment, the disease invariably recurs, even after the transplantation of autologous hematopoietic stem cells (ASCT). Biological processes leading to a pathological myeloma clone and the mechanisms of further evolution of the disease are far from complete understanding. Genetically, MM is a complex disease that demonstrates a high level of heterogeneity. Myeloma genomes carry numerous genetic changes, including structural genome variations and chromosomal gains and losses, and these changes occur in combinations with point mutations affecting various cellular pathways, including genome maintenance. MM genome instability in its extreme is manifested in mutation <i>kataegis</i> and complex genomic rearrangements: chromothripsis, templated insertions, and chromoplexy. Chemotherapeutic agents used to treat MM add another level of complexity because many of them exacerbate genome instability. Genome abnormalities are driver events and deciphering their mechanisms will help understand the causes of MM and play a pivotal role in developing new therapies.https://www.mdpi.com/2072-6694/13/23/5949multiple myelomagenome instabilitytranslocationschromothripsis<i>kataegis</i>editing deaminases |
| spellingShingle | Anna Y. Aksenova Anna S. Zhuk Artem G. Lada Irina V. Zotova Elena I. Stepchenkova Ivan I. Kostroma Sergey V. Gritsaev Youri I. Pavlov Genome Instability in Multiple Myeloma: Facts and Factors Cancers multiple myeloma genome instability translocations chromothripsis <i>kataegis</i> editing deaminases |
| title | Genome Instability in Multiple Myeloma: Facts and Factors |
| title_full | Genome Instability in Multiple Myeloma: Facts and Factors |
| title_fullStr | Genome Instability in Multiple Myeloma: Facts and Factors |
| title_full_unstemmed | Genome Instability in Multiple Myeloma: Facts and Factors |
| title_short | Genome Instability in Multiple Myeloma: Facts and Factors |
| title_sort | genome instability in multiple myeloma facts and factors |
| topic | multiple myeloma genome instability translocations chromothripsis <i>kataegis</i> editing deaminases |
| url | https://www.mdpi.com/2072-6694/13/23/5949 |
| work_keys_str_mv | AT annayaksenova genomeinstabilityinmultiplemyelomafactsandfactors AT annaszhuk genomeinstabilityinmultiplemyelomafactsandfactors AT artemglada genomeinstabilityinmultiplemyelomafactsandfactors AT irinavzotova genomeinstabilityinmultiplemyelomafactsandfactors AT elenaistepchenkova genomeinstabilityinmultiplemyelomafactsandfactors AT ivanikostroma genomeinstabilityinmultiplemyelomafactsandfactors AT sergeyvgritsaev genomeinstabilityinmultiplemyelomafactsandfactors AT youriipavlov genomeinstabilityinmultiplemyelomafactsandfactors |