TY - JOUR

T1 - Genome Instability in Multiple Myeloma: Facts and Factors

AU - Aksenova , Anna Y.

AU - Zhuk, Anna S.

AU - Lada, Artem G.

AU - Zotova, Irina V.

AU - Stepchenkova, Elena I.

AU - Kostroma , Ivan I.

AU - Gritsaev, Sergey V.

AU - Pavlov , Youri I.

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/11/26

Y1 - 2021/11/26

N2 - 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 kataegis 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.

AB - 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 kataegis 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.

KW - Chromothripsis

KW - DNA repair

KW - Editing deaminases

KW - Genome instability

KW - Kataegis

KW - Multiple myeloma

KW - Translocations

UR - http://www.scopus.com/inward/record.url?scp=85120866655&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/d48fca75-f193-3d39-a2db-016f2701fcb2/

U2 - 10.3390/cancers13235949

DO - 10.3390/cancers13235949

M3 - Review article

C2 - 34885058

VL - 13

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 23

M1 - 5949

ER -