Síndromes mielodisplàstiques

  • Solé Lab Juny 2022
ICO - German Trias i Pujol

Josep Carreras Leukaemia Research Institute 

Can Ruti Campus

Ctra de Can Ruti, Camí de les Escoles s/n

08916 Badalona, Barcelona, Spain





MDS are a heterogeneous group of haematological stem cell disorders resulting in bone marrow failure and blood cytopenias. The severity of the disease depends on a variety of biological factors that translate into a spectrum of symptoms with a profound impact on the patient’s quality of life and survival. A third of MDS patients will die after progressing to Acute Myeloid Leukaemia (AML). The remaining two thirds of patients will suffer from a combination of chronic anaemia, recurrent infections and bleeding episodes and will die from complications associated with cytopenias. MDS is one of the most common haematological malignancies of the elderly and its prevalence is increasing. Our research is focused in unravelling the heterogeneity of Myelodysplastic Syndromes (MDS) beyond symptomatic and morphological description. Despite recent scientific advances in the field, there are still no clear disease markers which facilitate diagnosis and prognosis in clinical practice. No single genetic aberration is common to all subtypes or specific to MDS and patients present varying proportions of abnormal cells with different genetic defects. A more detailed knowledge of the genome of leukemic cells will allow us to make more informed medical decisions, to initiate appropriate therapies earlier, to achieve higher probability of successful treatment resulting in better targeted therapies.


Our laboratory is focused in sample processing from myeloid disease related patients and its data integration. Samples of newly diagnosed patients and successive follows up will be processed according to a mix of state-of-art and clinically routine techniques:

- Single Nucleotide Polymorphism microarray (SNP arrays)
- Whole-Genome Sequencing
- Whole-Exome Sequencing
- Targeted sequencing to determine the mutational landscape
- Epigenetic profiling including DNA methylation and microRNAs expression

Clinical routine techniques:
- Cytogenetics of bone marrow and peripheral blood cells
- Fluorescence in situ hybridization (FISH)
- Flow cytometry


Dr. Consuelo del Cañizo, Dra. María Diez del Campelo, Hospital Clínico de Salamanca, Spain
Dr. José Cervera, Hospital la Fe, Valencia, Spain
Dr. Jesús Mª Hernández, Hospital Clínico de Salamanca, Spain
Dr. Juan Cruz Cigudosa, CNIO, Madrid, Spain
Dr. María José Calasanz, Universidad de Navarra, Pamplona, Spain
Grupo Cooperativo Español de Citogenética Hematológica (GCECGH)
Grupo Español de Síndromes Mielodisplásicos (GSMD)
Groups belonging to the Cancer Centres Network of Spain

Dr. Alan List, Moffit Cancer Canter Tampa, Florida, USA
Dr. Benjaminm Ebert, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
Dr. Detlef Haase. Clinics of Hematology and Medical Oncology Clinics of Hematology and Medical Oncology, Göttingen, Germany
Professor Ghulam Mufti, King´s College Hospital NHS Foundation Trust, London, Great Britain
Dr. Jaroslav Maciejewski, Cleveland Clinic. Cleveland, USA
Dr. Rafael Bejar, UCSD Moores Cancer Center, La Jolla, USA.
Dr. Udayakumar Achandira. Sultan Qaboos University. Oman.
International Working Group for the Prognosis of MDS (IWG-PM)
International Working Group on SMZL


Francesc SoléF_sole_3XICO - Germans Trias i Pujol - Campus Coordinator
Mar MalloMmallo_3xCore Facility Leader
Pamela AchaPACha3XPostdoctoral Researcher
Oriol CalveteOriol CalvetePostdoctoral Researcher
Javier GrauPostdoctoral Researcher
Ana ManzanaresAna ManzanaresTechnician

Selected publications

Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Tommaso Matteuzzi, Claudia Sala, Ettore Mosca, Chiara Chiereghin, Noemi Di Nanni, Matteo Gnocchi, Matteo Zampini, Marianna Rossi, Giulia Maggioni, Alberto Termanini, Emanuele Angelucci, Massimo Bernardi, Lorenza Borin, Benedetto Bruno, Francesca Bonifazi, Valeria Santini, Andrea Bacigalupo, Maria Teresa Voso, Esther Oliva, Marta Riva, Marta Ubezio, Lucio Morabito, Alessia Campagna, Claudia Saitta, Victor Savevski, Enrico Giampieri, Daniel Remondini, Francesco Passamonti, Fabio Cicer, Niccolò Bolli, Alessandro Rambaldi, Wolfgang Kern, Shahram Kordasti, Francesc Sole, Laura Palomo, Guillermo Sanz, Armando Santoro, Uwe Platzbecker, Pierre Fenaux, Luciano Milanesi, Torsten Haferlach, Gastone Castellani, Matteo G Della Porta

Classification and Personalized Prognostic Assessment on the Basis of Clinical and Genomic Features in Myelodysplastic Syndromes

J Clin Oncol . 2021 Feb 4;JCO2001659. 4 Feb 2021, .
Purpose: Recurrently mutated genes and chromosomal abnormalities have been identified in myelodysplastic syndromes (MDS). We aim to integrate these genomic features into disease classification and prognostication. Methods: We retrospectively enrolled 2,043 patients. Using Bayesian networks and Dirichlet processes, we combined mutations in 47 genes with cytogenetic abnormalities to identify genetic associations and subgroups. Random-effects Cox proportional hazards multistate modeling was used for developing prognostic models. An independent validation on 318 cases was performed. Results: We identify eight MDS groups (clusters) according to specific genomic features. In five groups, dominant genomic features include splicing gene mutations (SF3B1, SRSF2, and U2AF1) that occur early in disease history, determine specific phenotypes, and drive disease evolution. These groups display different prognosis (groups with SF3B1 mutations being associated with better survival). Specific co-mutation patterns account for clinical heterogeneity within SF3B1- and SRSF2-related MDS. MDS with complex karyotype and/or TP53 gene abnormalities and MDS with acute leukemia-like mutations show poorest prognosis. MDS with 5q deletion are clustered into two distinct groups according to the number of mutated genes and/or presence of TP53 mutations. By integrating 63 clinical and genomic variables, we define a novel prognostic model that generates personally tailored predictions of survival. The predicted and observed outcomes correlate well in internal cross-validation and in an independent external cohort. This model substantially improves predictive accuracy of currently available prognostic tools. We have created a Web portal that allows outcome predictions to be generated for user-defined constellations of genomic and clinical features. Conclusion: Genomic landscape in MDS reveals distinct subgroups associated with specific clinical features and discrete patterns of evolution, providing a proof of concept for next-generation disease classification and prognosis.
Més informació
Pamela Acha, Laura Palomo, Francisco Fuster-Tormo, Bianca Xicoy, Mar Mallo, Ana Manzanares, Javier Grau, Silvia Marcé, Isabel Granada, Marta Rodríguez-Luaces, María Díez-Campelo, Lurdes Zamora, Francesc Solé

Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach

Cancers 2021, 13(4), 841 17 Feb 2021, .
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be treated with lenalidomide. During the last decade, single cell (SC) analysis has emerged as a powerful tool to decipher clonal architecture and to further understand cancer and other diseases at higher resolution level compared to bulk sequencing techniques. In this study, a SC approach was used to analyze intratumoral heterogeneity in four patients with MDS del(5q). Single CD34+CD117+CD45+CD19- bone marrow hematopoietic stem progenitor cells were isolated using the C1 system (Fluidigm) from diagnosis or before receiving any treatment and from available follow-up samples. Selected somatic alterations were further analyzed in SC by high-throughput qPCR (Biomark HD, Fluidigm) using specific TaqMan assays. A median of 175 cells per sample were analyzed. Inferred clonal architectures were relatively simple and either linear or branching. Similar to previous studies based on bulk sequencing to infer clonal architecture, we were able to observe that an ancestral event in one patient can appear as a secondary hit in another one, thus reflecting the high intratumoral heterogeneity in MDS del(5q) and the importance of patient-specific molecular characterization.
Palomo L, Ibáñez M, Abáigar M, Vázquez I, Álvarez S, Cabezón M, Tazón-Vega B, Rapado I, Fuster-Tormo F, Cervera J, Benito R, Larrayoz MJ, Cigudosa JC, Zamora L, Valcárcel D, Cedena MT, Acha P, Hernández-Sánchez JM, Fernández-Mercado M, Sanz G, Hernández-Rivas JM, Calasanz MJ, Solé F, Such E

Spanish Guidelines for the use of targeted deep sequencing in myelodysplastic syndromes and chronic myelomonocytic leukaemia.

Br. J. Haematol. 16 Oct 2019, . Epub 16 Oct 2019
The landscape of medical sequencing has rapidly changed with the evolution of next generation sequencing (NGS). These technologies have contributed to the molecular characterization of the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), through the identification of recurrent gene mutations, which are present in >80% of patients. These mutations contribute to a better classification and risk stratification of the patients. Currently, clinical laboratories include NGS genomic analyses in their routine clinical practice, in an effort to personalize the diagnosis, prognosis and treatment of MDS and CMML. NGS technologies have reduced the cost of large-scale sequencing, but there are additional challenges involving the clinical validation of these technologies, as continuous advances are constantly being made. In this context, it is of major importance to standardize the generation, analysis, clinical interpretation and reporting of NGS data. To that end, the Spanish MDS Group (GESMD) has expanded the present set of guidelines, aiming to establish common quality standards for the adequate implementation of NGS and clinical interpretation of the results, hoping that this effort will ultimately contribute to the benefit of patients with myeloid malignancies.
Més informació
Palomo L, Meggendorfer M, Hutter S, Twardziok S, Ademà V, Fuhrmann I, Fuster-Tormo F, Xicoy B, Zamora L, Acha P, Kerr CM, Kern W, Maciejewski JP, Sole, F.

Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms

Blood . 2020 Oct 15;136(16):1851-1862 15 Oct 2020, .
More than 90% of patients with myelodysplastic/myeloproliferative neoplasms (MDSs/MPNs) harbor somatic mutations in myeloid-related genes, but still, current diagnostic criteria do not include molecular data. We performed genome-wide sequencing techniques to characterize the mutational landscape of a large and clinically well-characterized cohort including 367 adults with MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 119), atypical chronic myeloid leukemia (aCML; n = 71), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 71), and MDS/MPN unclassifiable (MDS/MPN-U; n = 106). A total of 30 genes were recurrently mutated in ≥3% of the cohort. Distribution of recurrently mutated genes and clonal architecture differed among MDS/MPN subtypes. Statistical analysis revealed significant correlations between recurrently mutated genes, as well as genotype-phenotype associations. We identified specific gene combinations that were associated with distinct MDS/MPN subtypes and that were mutually exclusive with most of the other MDSs/MPNs (eg, TET2-SRSF2 in CMML, ASXL1-SETBP1 in aCML, and SF3B1-JAK2 in MDS/MPN-RS-T). Patients with MDS/MPN-U were the most heterogeneous and displayed different molecular profiles that mimicked the ones observed in other MDS/MPN subtypes and that had an impact on the outcome of the patients. Specific gene mutations also had an impact on the outcome of the different MDS/MPN subtypes, which may be relevant for clinical decision-making. Overall, the results of this study help to elucidate the heterogeneity found in these neoplasms, which can be of use in the clinical setting of MDS/MPN.
Més informació
Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, Yoshizato T, Shiozawa Y, Saiki R, Malcovati L, Levine MF, Arango JE, Zhou Y,, Solé, F, Cargo CA, Haase D, Creignou M, Germing U, Zhang Y, Gundem G, Sarian A, van de Loosdrecht AA, Jädersten M, Tobiasson M, Kosmider O, Follo MY, Thol F, Pinheiro RF, Santini V, Kotsianidis I, Boultwood J, Santos FPS, Schanz J, Kasahara S, Ishikawa T, Tsurumi H, Takaori-Kondo A, Kiguchi T, Polprasert C, Bennett JM, Klimek VM, Savona MR, Belickova M, Ganster C, Palomo L, Sanz G, Ades L, Della Porta MG, Smith AG, Werner Y, Patel M, Viale A, Vanness K, Neuberg DS, Stevenson KE, Menghrajani K, Bolton KL, Fenaux P, Pellagatti A, Platzbecker U, Heuser M, Valent P, Chiba S, Miyazaki Y, Finelli C, Voso MT, Shih LY, Fontenay M, Jansen JH, Cervera J, Atsuta Y, Gattermann N, Ebert BL, Bejar R, Greenberg PL, Cazzola M, Hellström-Lindberg E, Ogawa S, Papaemmanuil E.

Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Nat Med . 2020 Oct;26(10):1549-1556. 3 Ago 2020, .
Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6-8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response.
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Current projects


Responsable:Francesc Solé
Data d'inici:01/01/2019
Data de finalització:31/12/2022

CELGENE LOW RISK: Monitoring mutational burden in low risk MDS patients using sequential peripheral blood samples

Responsable:Francesc Solé
Codi:Celgene PI-13279-IIT
Data d'inici:01/01/2019
Data de finalització:31/12/2022

Dissecting the mechanisms of clonal expansion in del(5q) myelodysplastic syndrome to selectively target the disease-initiating hematopoietic stem cells

Responsable:Francesc Solé
Data d'inici:01/10/2021
Data de finalització:30/09/2024

Caracterització genètica de les neoplàsies mieloides associades a tractament(Therapy related myeloid neoplasms, TRMN), finançat per l'Institut de Salut Carlos III (ISCIII) i cofinançat per la Unió Europea

Responsable:Francesc Solé
Data d'inici:01/01/2021
Data de finalització:31/12/2023

Previous projects

Translational Research on Rare Cancers

Responsable:Francesc Solé
Data d'inici:01/12/2018
Data de finalització:21/01/2020

Estudio de los cambios genéticos de pacientes con síndrome mielodisplásico (SMD) 5q- tratados con Lenalidomida. Determinación de los cambios responsables de la respuesta al tratamiento”.

Responsable:Francesc Solé
Codi:PI 11/0210
Data d'inici:01/09/2012
Data de finalització:31/12/2014

Subprograma RETICS 2012.

Responsable:Francesc Solé
Data d'inici:01/01/2013
Data de finalització:30/04/2017

Mutational analysis (NGS) in MDS 5q- and non 5q- patients treated with Lenalidomide. Relation with their response to treatment.

Responsable:Francesc Solé
Codi:Celgene International
Data d'inici:01/01/2014
Data de finalització:31/12/2016

Grups de Recerca Reconeguts per la Generalitat de Catalunya (SGR-2014)

Responsable:Francesc Solé
Codi:2014 SGR 225-GRE
Data d'inici:01/11/2014
Data de finalització:30/04/2017

Combined application of conventional cytogenetics, FISH, SNP arrays and NGS technology in the clinical practice of Myelodysplastic Syndromes. Diagnostic, pathogenetic, prognostic and therapeutic implications (Co-Investigador Principal con Detlef Haase)

Responsable:Francesc Solé
Codi:AR 14/34
Data d'inici:01/01/2014
Data de finalització:31/12/2016

Estudio en subclones de los cambios genéticos de pacientes con síndrome mielodisplásico (SMD) 5q- tratados con Lenalidomida. s cambios genéticos de pacientes con síndrome mielodisplásico (SMD) 5q- tratados con Lenalidomida”. Equipo Investigador: Mar Mallo, Laura Palomo, Silvia Marce, Javier Grau, Blanxa Xicoy

Responsable:Francesc Solé
Codi:PI 14/00013
Data d'inici:01/01/2015
Data de finalització:31/12/2017

IDH1/2 Mutational analysis in AML patients. Diagnosis and follow-up.Equipo Investigador: Mar Mallo, Laura Palomo, Lurdes Zamora, Marta Pratcorona, Jordi Esteve, Josep Nomdedeu, Jordi Sierra

Responsable:Francesc Solé
Codi:Celgene N/A-NI-AML-PI-007344
Data d'inici:01/01/2016
Data de finalització:31/12/2018

Celgene Myeloma Projecte F Sole

Responsable:Francesc Solé
Data d'inici:31/12/2014
Data de finalització:31/12/2018

Aplicación de la secuenciación masiva (NGS) en el diagnóstico y pronóstico de síndromes mielodisplasicos/neoplasias mieloproliferativas

Responsable:Francesc Solé
Data d'inici:01/01/2018
Data de finalització:31/08/2020

2017-AGAUR-01084 Agència de Gestió d'Ajuts Universitaris i de Recerca, Grups de Recerca de Catalunya (SGR)

Responsable:Francesc Solé
Codi:2017 SGR 288
Data d'inici:01/01/2017
Data de finalització:31/12/2019

Proyectos de Investigación en Salud

Responsable:Francesc Solé
Data d'inici:31/12/2014
Data de finalització:31/12/2018