Optical genome mapping in myelofibrosis: enhancing prognostic accuracy through high-resolution genomic profiling

Accurate genomic stratification is essential for guiding therapeutic decisions in myelofibrosis (MF), particularly regarding allogeneic stem cell transplant. Conventional chromosome banding analysis (CBA), however, has limited resolution and provides an informative karyotype in only about half of patients with MF. In a prospective series of 107 patients with primary or secondary MF, we compared optical genome mapping (OGM) plus targeted next-generation sequencing with CBA. OGM generated interpretable cytogenetic data for every sample, whereas CBA succeeded in fewer than half. In addition, OGM revealed structurally complex alterations and copy-neutral loss of heterozygosity that conventional methods missed. Integration of OGM results into contemporary prognostic models, including DIPSS-plus, GIPSS, and MIPSS70-plus version 2.0 (MIPSS70v2), refined risk allocation across the cohort. The greatest impact was observed for the transplant-oriented MIPSS70v2: the proportion of patients assigned to high-risk or very-high-risk categories increased from 19% with CBA alone to 36% after incorporating OGM findings. Incorporation of OGM data enabled full risk stratification of all 57 individuals with nonevaluable CBA karyotypes; 16 were assigned directly to the high-risk or very high MIPSS70v2 risk categories, a reclassification with immediate implications for transplant referral and follow-up intensity. This study represents the largest prospective evaluation of OGM in MF, demonstrating that OGM overcomes the limitations of CBA, uncovers clinically relevant cryptic alterations, and refines prognostic stratification. These findings support integrating OGM with targeted sequencing as a step toward precision medicine in MF.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2025-10-28
DOI
https://doi.org/10.1182/bloodadvances.2025017980
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Optical genome mapping in myelofibrosis: enhancing prognostic accuracy through high-resolution genomic profiling

Alberto Álvarez‐Larrán, Álvaro Díaz‐González, Ruth Stuckey, Eduardo Arellano‐Rodrigo et al.
Blood Advances
Myeloproliferative Neoplasms: Diagnosis and Treatment
article

Optical genome mapping in myelofibrosis: enhancing prognostic accuracy through high-resolution genomic profiling

Alberto Álvarez‐Larrán, Álvaro Díaz‐González, Ruth Stuckey, Eduardo Arellano‐Rodrigo, Nerea Uresandi, Marta Salido Galeote, Adrián Segura-Díaz, Elvira Mora, Blanca Espinet, Marta Garrote, Irene Pastor‐Galán, Eva Villamón, Esperanza Such, Juan Carlos Hernández‐Boluda, Cristian García-Ruiz, Santiago Furió, Gonzalo Carreño‐Tarragona, Rosa María Ayala, Neus Torres Hernández, Noemí Álvarez, Patricia Vélez, Adela Cisneros, Gayane Avetisyan, Nagore Argoitia-Ituarte, Jose Antonio Domingo-Monfort
article en

Abstract

Accurate genomic stratification is essential for guiding therapeutic decisions in myelofibrosis (MF), particularly regarding allogeneic stem cell transplant. Conventional chromosome banding analysis (CBA), however, has limited resolution and provides an informative karyotype in only about half of patients with MF. In a prospective series of 107 patients with primary or secondary MF, we compared optical genome mapping (OGM) plus targeted next-generation sequencing with CBA. OGM generated interpretable cytogenetic data for every sample, whereas CBA succeeded in fewer than half. In addition, OGM revealed structurally complex alterations and copy-neutral loss of heterozygosity that conventional methods missed. Integration of OGM results into contemporary prognostic models, including DIPSS-plus, GIPSS, and MIPSS70-plus version 2.0 (MIPSS70v2), refined risk allocation across the cohort. The greatest impact was observed for the transplant-oriented MIPSS70v2: the proportion of patients assigned to high-risk or very-high-risk categories increased from 19% with CBA alone to 36% after incorporating OGM findings. Incorporation of OGM data enabled full risk stratification of all 57 individuals with nonevaluable CBA karyotypes; 16 were assigned directly to the high-risk or very high MIPSS70v2 risk categories, a reclassification with immediate implications for transplant referral and follow-up intensity. This study represents the largest prospective evaluation of OGM in MF, demonstrating that OGM overcomes the limitations of CBA, uncovers clinically relevant cryptic alterations, and refines prognostic stratification. These findings support integrating OGM with targeted sequencing as a step toward precision medicine in MF.

Blood AdvancesVol. 10(2)
Universidad Complutense de Madrid (ES), Hospital Universitari i Politècnic La Fe (ES), Research Institute Hospital 12 de Octubre (ES), Josep Carreras Leukaemia Research Institute (ES), Hospital Clínico Universitario de Valencia (ES), Hospital Universitario de Gran Canaria Doctor Negrín (ES), Biogipuzkoa Health Research Institute (ES), Centro Nacional de Epidemiología (ES), Institut Català d'Oncologia (ES), Hospital Clínic de Barcelona (ES), National Clinical Research (US), Hospital Del Mar (ES), Fundación Josep Carreras Contra la Leucemia (ES), Hospital General Universitario de Albacete (ES), Complejo Hospitalario Universitario de Albacete (ES), INCLIVA Health Research Institute (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Instituto de Investigación Sanitaria La Fe (ES)
Openalex Percentile: Top 57%
Myeloproliferative Neoplasms: Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.