Dolors Colomer

• PhD
• Consultant at Hospital Clínic de Barcelona

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of monoclonal mature B lymphocytes in peripheral blood, bone marrow, lymphoid tissues, and extranodal sites. Genes involved in RNA splicing such as SF3B1 and U1 are frequently mutated in CLL, leading to altered splicing and generation of tumor neoepitopes. To study the impact o...

The presence of a monoclonal protein detected by serum immunofixation electrophoresis (sIFE) has been reported as an adverse prognostic factor in chronic lymphocytic leukemia (CLL). However, the genetic underpinning of this finding has not been studied. We retrospectively studied 97 CLL patients with simultaneous information on sIFE and genetic alt...

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, is a paradigm of the contribution of the immune tumor microenvironment (TME) to disease onset, progression, and therapy resistance. To recreate the cellular components, signaling cues, and the physical environment, we have optimized the generation of Patient Derived Lymphoma T...

Mantle cell lymphoma (MCL) is considered one of the most aggressive B-cell lymphoid neoplasms. The transcription factor SOX11 is aberrantly expressed in conventional aggressive MCL but is either negative or very weakly expressed in the leukemic non-nodal MCL subtype, which has a predominantly indolent clinical evolution. SOX11 is a key MCL driver t...

Chronic lymphocytic leukemia (CLL) has heterogeneous biological characteristics influenced in part by the interactions of tumor cells with the tumor microenvironment (TME). The lymph node (LN) represents a critical niche for in vivo CLL proliferation and development of treatment resistance. Traditional 2D cultures fall short in replicating the TME,...

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. Although achieving a complete response with first-line treatment, most of the patients eventually relapse, which worsens the prognosis and increases the risk of histological transformation to aggressive lymphoma. Therefore, there is the need to better stratify patients at diagnos...

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular derm...

The 2022 WHO revision and the ICC classification have recently modified the diagnostic criteria for chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia. However, there is no consensus on whether CMML with NPM1 mutation (NPM1mut) should be diagnosed as AML. Nowadays, it is a subject of discussion because of its diagnostic and therapeut...

Two new diagnostic classifications of acute myeloid leukemia (AML) were published in 2022 to update current knowledge on disease biology. In previous 2017-edition categories of AML with myelodysplasia-related changes, AML was not otherwise specified, but AML with mutated RUNX1 experienced profound changes. We performed whole exome sequencing on a c...

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. Despite most patients achieve a complete response with first-line treatment, an important fraction of them relapse, which may worsen the prognosis and increase the risk of a histological transformation to aggressive lymphoma. Therefore, there is a need to better stratify the pati...

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular derm...

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL...

Non-acute myeloid neoplasms (MNs) with NPM1 mutations (NPM1mut-MNs) pose a diagnostic and therapeutic dilemma, primarily manifesting as chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). The classification and treatment approach for these conditions as acute myeloid leukemia (AML) are debated. We describe eight cases of aty...

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequenc...

Failure of immunotherapy after applying checkpoint inhibitors or CAR-T cells is linked to T cell exhaustion. Here, we explored the T cell landscape in chronic lymphocytic leukemia (CLL) using blood, bone marrow and lymph node samples of patients and spleen samples of a CLL mouse model. By single-cell RNA-sequencing, mass cytometry (CyTOF), and mult...

To elucidate the role of splanchnic vein thrombosis (SVT) and genomic characteristics in prognosis and survival, we compared patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting SVT at diagnosis (n = 69, median age 43 years) or during follow-up (n = 21, median age 46 years) to a sex- and age-matched control group of PV/...

Understanding the evolution patterns in patients diagnosed with acute myeloid leukemia (AML) after therapy is relevant due to the dismal outcome still present in refractory or relapsed AML patients. We performed a retrospective, single-center study to evaluate the mutation profile in paired samples obtained at the time of diagnosis and at the onset...

Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical behavior. In 5-10% of patients the disease transforms into a diffuse large-B cell lymphoma known as Richter transformation (RT), which is associated with dismal prognosis. Here, we aimed to establish patient-derived xenograft (PDX) models to study the molecular fe...

Introduction Acute myeloid leukemia (AML) is a biologically highly heterogeneous disease. An increasing number of genetic abnormalities responsible for its pathogenesis are being incorporated in latest classifications to refine AML diagnosis. Myelodysplasia-related AML (AML-MR) is a broad category defined by mutations in a significant number of gen...

Recently modified diagnostic criteria for chronic myelomonocytic leukaemia (CMML) have lowered the cut‐off for absolute monocytosis. In the largest series to date, we have analysed 313 CMML patients, including 104 with oligomonocytic (OM)‐CMML. Five‐year survival was longer for OM‐CMML than for other patients (p < 0.001). Multivariate analysis iden...

The t(14;19)(q32;q13) often juxtaposes BCL3 with IGH resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3-rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neo...

Splicing factor 3B subunit 1 (SF3B1) is involved in pre-mRNA branch site recognition and is the target of antitumor-splicing inhibitors. Mutations in SF3B1 are observed in 15% of patients with chronic lymphocytic leukemia (CLL) and are associated with poor prognosis, but their pathogenic mechanisms remain poorly understood. Using deep RNA-sequencin...

Myelofibrosis (MF) is a heterogeneous disease regarding its mutational landscape, clinical presentation, and outcomes. The aim of our work is to evaluate the genomic classification of MF considering whether it is primary or secondary. One-hundred seventy-five patients, 81 with primary MF (PMF) and 94 with secondary MF (SMF) were hierarchically allo...

Germline predisposition in acute myeloid leukemia (AML) has gained importance in recent years due to a non-negligible frequency and impact on management of patients and their relatives. Risk alleles for AML development may be present in patients without a clinical suspicion of hereditary hematologic malignancy syndrome. In this study we investigate...

In recent years, major advances in the understanding of acute myeloid leukemia (AML) pathogenesis, together with technological progress, have led us into a new era in the diagnosis and follow-up of patients with AML. A combination of immunophenotyping, cytogenetic and molecular studies are required for AML diagnosis, including the use of next-gener...

Post-transplant lymphoproliferative disorders (PTLD) represent a broad spectrum of lymphoid proliferations, frequently associated with Epstein-Barr Virus (EBV) infection. The molecular profile of pediatric monomorphic PTLDs (mPTLD) has not been elucidated and it is unknown whether they display similar genetic features as their counterpart in adult...

Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-der...

The genetic mechanisms associated with splenic marginal zone lymphoma transformation (SMZL-T) are not well defined. We studied 41 SMZL patients that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 pati...

Mantle cell lymphoma (MCL), a rare and aggressive B cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-der...

Failure of cancer immunotherapy is linked to T cell exhaustion. To decipher the underlying mechanisms, we explored the T cell landscape in blood, bone marrow and lymph node samples of patients with chronic lymphocytic leukemia (CLL), and spleen samples of a CLL mouse model. By single-cell RNA-sequencing, mass cytometry (CyTOF), and multiplex image...

Waldenström macroglobulinaemia (WM) is characterized by recurrent somatic mutations in MYD88 and CXCR4 genes. However, limitations arise when analysing these mutations in IgM monoclonal gammopathy of undetermined significance (MGUS) or smouldering WM (SWM) given the lower tumour load. Here, we used droplet digital polymerase chain reaction (ddPCR)...

Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens...

Background: T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm closely related to T-cell acute lymphoblastic leukaemia (T-ALL). Despite their similarities, and contrary to T-ALL, studies on paediatric T-LBL are scarce and, therefore, its molecular landscape has not yet been fully elucidated. Thus, the aims of this study were to charac...

Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and function...

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material...

Several studies have reported that chronic myeloid leukaemia (CML) patients expressing e14a2 BCR::ABL1 have a faster molecular response to therapy compared to patients expressing e13a2. To explore the reason for this difference we undertook a detailed technical comparison of the commonly used Europe Against Cancer (EAC) BCR::ABL1 reverse transcript...

Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we present a comprehensive census of cell types forming the human tonsil by applying single-cell transcriptome, epigenome, proteome and adaptive immune repertoire sequencing as well as spatial transcriptom...

Introduction: Clonal evolution drives cancer development due to the emergence and/or selection of proliferatively advantageous subclones. Its understanding may facilitate the design of anticipation-based management strategies. Richter transformation (RT) is a paradigmatic tumor evolution in which chronic lymphocytic leukemia (CLL), an indolent neop...

The genetic landscape of post-transplant lymphoproliferative disorders (PTLD) in pediatric population has not been fully elucidated. This absence of information raises the question whether therapeutic strategies should be the same as for their counterparts in immunocompetent (IC) patients. The aim of this study was to characterize genetically and i...

Pediatric nodal marginal zone lymphoma (PNMZL) is an uncommon B-cell neoplasm affecting mainly male children and young adults. This indolent lymphoma has distinct characteristics that differ from conventional nodal marginal zone lymphoma (NMZL). Clinically, it shows overlapping features with pediatric-type follicular lymphoma (PTFL). To explore the...

Background T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm closely related to T-cell acute lymphoblastic leukaemia (T-ALL). Despite their similarities, and contrary to T-ALL, studies on pediatric T-LBL are scarce and, therefore, its molecular landscape has not been fully elucidated yet. Procedure To characterize the genetic and mole...

Serum soluble CD23 (sCD23) levels have been acknowledged as a prognostic factor in patients with chronic lymphocytic leukemia (CLL), but their potential relevance has not been analyzed in recent times. We retrospectively studied 338 CLL, small lymphocytic lymphoma, or CLL‐type monoclonal B‐cell lymphocytosis patients from a single institution, with...

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm treated with tyrosine kinase inhibitors (TKIs). Although survival rates have improved, response to these treatments is highly heterogeneous. Variations in response rates may be due to different causes such as, treatment adherence, mutations in the BCR-ABL1 gene, clonal evolution and am...

T cell exhaustion limits anti-tumor immunity and responses to immunotherapy. Here, we explored the microenvironmental signals regulating T cell exhaustion using a model of chronic lymphocytic leukemia (CLL). Single-cell analyses identified a subset of PD-1hi, functionally impaired CD8⁺ T cells that accumulated in secondary lymphoid organs during di...

BACKGROUND: MYD88 L265P mutation is highly prevalent in IgM monoclonal gammopathy of undetermined significance (MGUS), smoldering Waldenström macroglobulinemia (SWM) and symptomatic WM. Allele-specific PCR (AS-PCR) has been used routinely to assess MYD88 mutation; however, with the advent of more precise high-throughput technologies such as droplet...

Genome-wide association studies identified a single-nucleotide polymorphism (SNP) affecting the transcription factor Eomesodermin (EOMES) associated with a significantly increased risk to develop chronic lymphocytic leukemia (CLL). Epigenetic analyses, RNA sequencing, and flow cytometry revealed that EOMES is not expressed in CLL cells, but in CD8+...

Purpose: approximately 1-2% of chronic myeloid leukemia (CML) patients harbor atypical BCR-ABL1 transcripts that cannot be monitored by real-time quantitative PCR (RT-qPCR) using standard methodologies. Within the European Treatment and Outcome Study (EUTOS) for CML we established and validated robust RT-qPCR methods for these patients. Methods:...

We describe 36 patients with splenic marginal zone lymphoma (SMZL) with transformation (SMZL‐T), including 15 from a series of 84 patients with SMZL diagnosed at the Hospital Clinic of Barcelona (HCB) and 21 diagnosed with SMZL‐T in other centres. In the HCB cohort, the cumulative incidence of transformation at 5 years was 15%. Predictors for trans...

Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples and HK follicular dendritic cells (FDC) to mimic the germinal center, together with mouse models, we have analyzed the three-way crosstalk of FL-FDC-macrophages and...

Chromosomal translocations in chronic lymphocytic leukemia (CLL) are very rare, and therefore systematic analysis of large series of cases are needed to allow the identification of recurrent rearrangements, breakpoints involved, and target genes. The aims of the present study were to identify new translocations and their clinical impact and to esta...

T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorder of natural killer (NK) cells are two infrequent diseases characterized by clonal expansions of cytotoxic T lymphocytes and NK cells, respectively. Somatic mutations of STAT3 are involved in the pathogenesis of these entities. We describe the clinicobiologic...

The transcription factor eomesodermin (EOMES) promotes interleukin (IL)-10 expression in CD4+ T cells, which has been linked to immunosuppressive and cytotoxic activities. We detected cytotoxic, programmed cell death protein-1 (PD-1) and EOMES co-expressing CD4+ T cells in lymph nodes (LNs) of patients with chronic lymphocytic leukemia (CLL) or dif...

Chronic lymphocytic leukemia (CLL) is characterized by a high degree of genetic variability and interpatient heterogeneity. In the last decade, novel alterations have been described. Some of them impact on the prognosis and evolution of patients. The approval of BTK inhibitors, PI3K inhibitors and Bcl-2 inhibitors has drastically changed the treatm...

We analyzed 171 patients with asymptomatic IgM monoclonal gammopathies (64 with IgM monoclonal gammopathy of undetermined significance—MGUS and 107 with smoldering Waldenström macroglobulinemia - SWM) who had a bone marrow (BM) evaluation performed at diagnosis. Abnormal free-light chain ratio (53% vs. 31%) and MYD88 mutation prevalence (66% vs. 30...

To investigate the three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia and mantle cell lymphoma patients, here we integrate in situ Hi-C and nine additional omics layers. Beyond conventional active (A) and inactive (B) compartments, we uncove...

Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. We used a platform f...

Robust protocols and automation now enable large-scale single-cell RNA and ATAC sequencing experiments and their application on biobank and clinical cohorts. However, technical biases introduced during sample acquisition can hinder solid, reproducible results, and a systematic benchmarking is required before entering large-scale data production. He...

Fifty-five cases of t(14;18)− follicular lymphoma (FL) were genetically characterized by targeted sequencing and copy number (CN) arrays. t(14;18)− FL predominated in women (M/F 1:2); patients often presented during early clinical stages (71%), and had excellent prognoses. Overall, t(14;18)− FL displayed CN alterations (CNAs) and gene mutations car...

Despite idelalisib approval in relapsed follicular lymphoma (FL), a complete characterization of the immunomodulatory consequences of phosphatidylinositol 3-kinase δ (PI3Kδ) inhibition, biomarkers of response, and potential combinatorial therapies in FL remain to be established. Using ex vivo cocultures of FL patient biopsies and follicular dendrit...

Background: Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. The pres...

Immunoglobulin (Ig) gene rearrangements and oncogenic translocations are routinely assessed during the characterization of B cell neoplasms and stratification of patients with distinct clinical and biological features, with the assessment done using Sanger sequencing, targeted next-generation sequencing, or fluorescence in situ hybridization (FISH)...

Chronic lymphocytic leukemia is a well-defined lymphoid neoplasm with very heterogeneous biological and clinical behavior. The last decade has been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease including mechanisms of genetic susceptibility, insights into the relevance of immunogenetic factors...

Background & Aims Myeloproliferative neoplasms (MPN) are the most frequent cause of non-tumoral non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology and detection of specific gene mutations. Next generation sequencing (NGS) allows the simultaneous evaluation of multiple...

The molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). The quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to front-line nilotinib was studied using data from 60 patients with chronic phase CML from t...

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with two molecular subtypes, conventional (cMCL) and leukemic non-nodal (nnMCL), that differ in their clinicobiological behavior. To identify the genetic/epigenetic alterations determining this diversity, we used whole-genome (n=61) and exome (n=21) seque...