Unraveling the chromosomal chaos: new insights into multiple myeloma thanks to genomic mapping
Researchers at ibs.GRANADA are using powerful genomic tools to reveal how DNA is altered in multiple myeloma, providing key information to personalize treatments and improve patient prognosis.
A team of Biosanitary Research Institute ibs.GRANADA He has used cutting-edge genomic technologies to delve into the complex genetic architecture of multiple myeloma and other hematological malignancies. His results reveal mechanisms that could decisively influence disease progression and response to treatment, opening new avenues toward more personalized medicine.
Hematologic malignancies, such as multiple myeloma or acute leukemias, are characterized by high genetic heterogeneity. This variability explains why patients with the same diagnosis can have very different prognoses and therapeutic responses. Understanding these differences is key to advancing toward more effective therapies tailored to each individual case.
To address this complexity, the ibs.GRANADA team, with professionals also affiliated with the Virgen de las Nieves University Hospital and the University of Granada, has employed two cutting-edge tools: optical genome mapping (OGM) and next-generation sequencing (NGS). These techniques allow for the highly accurate detection of both structural and numerical alterations in chromosomes, as well as point mutations in DNA, providing a comprehensive view of the tumor genome.
“Thanks to the combination of GMOs and NGS, we can observe in great detail how the tumor's genetic material is organized and how it changes over time. This information is essential to understanding why some patients respond better to certain therapies and others develop resistance,” he explains. Monica Bernal, group researcher A08-Immune Response and Cancer of the ibs.GRANADA and lead author of the studies.
The studies have made it possible to identify several genomic phenomena of particular relevance. Among them, hyperdiploidy stands out, an alteration associated with a better prognosis in certain patients. Cryptic rearrangements, undetectable by conventional cytogenetic techniques, have also been detected, as well as losses of heterozygosity without a change in copy number (copy-neutral LOH) in key genes such as TP53In addition, chromoanagenesis events have been observed, in which multiple catastrophic rearrangements drastically reorganize the tumor genome and can favor the emergence of clones with new biological properties and potential resistance to treatments.
Furthermore, these technologies allow tracking the clonal evolution of tumors throughout the course of the disease, detecting the emergence of new subclones and the progressive accumulation of genetic alterations that influence their clinical behavior.
The results reinforce the relevance of accurate genomic characterization in the diagnosis and management of hematological malignancies, in line with the recommendations of the World Health Organization (WHO), the International Consensus Classification (ICC) and the International Myeloma Working Group (IMWG).
This approach represents a significant step towards precision oncohematological medicine, which adapts therapeutic strategies to the genetic profile of each patient, with the aim of improving the prognosis and optimizing available treatments.
Bibliographic references:
- Jorge A. Palacios, Mónica Bernal, Jose R. Vílchez, Pilar Garrido, Pilar Jiménez, Juan F. Gutiérrez-Bautista, María C. Barrera-Aguilera, Lucía Ballesta, Teresa Rodríguez, María J. Olivares-Durán, and Francisco Ruiz-Cabello. Optical genome mapping reveals complex cytogenetic abnormalities in multiple myeloma. 2025 Jun 19. doi: 10.3324/haematol.2025.288008. Epub ahead of print. PMID: 40534500.
- Lucía Ballesta-Alcaraz, Mónica Bernal, Jose R. Vílchez, Jorge Palacios, Pilar Jiménez, Pilar Garrido, Juan F. Gutiérrez-Bautista, Francisco Ruiz-Cabello. Application of Optical Genome Mapping for the Diagnosis and Risk Stratification of Myeloid and Lymphoid Malignancies. Int. J. Mol. Sci. 2025 Jun 16;26(12):5763. doi: 10.3390/ijms26125763. PMID: 40565225; PMCID: PMC12192876.
