Síndromes mielodisplàstiques

  • Sole lab Mielodisplásicos 2021
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 Investigator
Oriol CalveteOriol CalvetePostdoctoral Investigator
Javier GrauPostdoctoral Investigator
Francisco FusterFfuster_3XPhD Student
Nuri De HaroNDeharo_3XTechnician
Ana ManzanaresAna ManzanaresTechnician

Selected publications

O. Molina, MA Abad,, Sole F, Menendez P

Aneuploidy in Cancer: Lessons from Acute Lymphoblastic Leukemia

Trends Cancer . 2020 Sep 17;S2405-8033(20)30240-5 17 Set 2020, .
Aneuploidy, the gain or loss of chromosomes in a cell, is a hallmark of cancer. Although our understanding of the contribution of aneuploidy to cancer initiation and progression is incomplete, significant progress has been made in uncovering the cellular consequences of aneuploidy and how aneuploid cancer cells self-adapt to promote tumorigenesis. Aneuploidy is physiologically associated with significant cellular stress but, paradoxically, it favors tumor progression. Although more common in solid tumors, different forms of aneuploidy represent the initiating oncogenic lesion in patients with B cell acute lymphoblastic leukemia (B-ALL), making B-ALL an excellent model for studying the role of aneuploidy in tumorigenesis. We review the molecular mechanisms underlying aneuploidy and discuss its contributions to B-ALL initiation and progression.
Més informació
Palomo L, Garcia O, Arnan M, Xicoy B, Fuster F, Cabezón M, Coll R, Ademà V, Grau J, Jiménez MJ, Pomares H, Marcé S, Mallo M, Millá F, Alonso E, Sureda A, Gallardo D, Feliu E, Ribera JM, Solé F, Zamora L

Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features.

Oncotarget 29 Jul 2016, . Epub 29 Jul 2016
Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC.
Més informació
Schneider RK, Ademà V, Heckl D, Järås M, Mallo M, Lord AM, Chu LP, McConkey ME, Kramann R, Mullally A, Bejar R, Solé F, Ebert BL

Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS.

Cancer Cell 13 Oct 2014, 26 (4) 509-20. Epub 18 Set 2014
The casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage, whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the nondeleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target.
Més informació
Mallo M, Del Rey M, Ibáñez M, Calasanz MJ, Arenillas L, Larráyoz MJ, Pedro C, Jerez A, Maciejewski J, Costa D, Nomdedeu M, Diez-Campelo M, Lumbreras E, González-Martínez T, Marugán I, Such E, Cervera J, Cigudosa JC, Alvarez S, Florensa L, Hernández JM, Solé F

Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations.

Br. J. Haematol. Jul 2013, 162 (1) 74-86. Epub 25 Abr 2013
Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide.
Més informació
Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, Granada I, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Valent P, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Faderl S, Pierce S, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D

New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.

J. Clin. Oncol. 10 Mar 2012, 30 (8) 820-9. Epub 13 Feb 2012
The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients.
Més informació
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Current projects


Responsable:Francesc Solé
Data d'inici:01/01/2019
Data de finalització:31/12/2021

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:31/12/2021

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

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