Research publications

Found 51 publicacions matching the indicated search criteria.
Genescà E, Lazarenkov A, Morgades M, Berbis G, Ruíz-Xivillé N, Gómez-Marzo P, Ribera J, Juncà J, González-Pérez A, Mercadal S, Guardia R, Artola MT, Moreno MJ, Martínez-López J, Zamora L, Barba P, Gil C, Tormo M, Cladera A, Novo A, Pratcorona M, Nomdedeu J, González-Campos J, Almeida M, Cervera J, Montesinos P, Batlle M, Vives S, Esteve J, Feliu E, Solé F, Orfao A, Ribera JM

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.

J Hematol Oncol 24 Jul 2018, 11 (1) 96. Epub 24 Jul 2018
Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.
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Martin R, Acha P, Ganster C, Palomo L, Dierks S, Fuster-Tormo F, Mallo M, Ademà V, Gómez-Marzo P, De Haro N, Solanes N, Zamora L, Xicoy B, Shirneshan K, Flach J, Braulke F, Schanz J, Kominowski A, Stromburg M, Brockmann A, Trümper L, Solé F, Haase D

Targeted deep sequencing of CD34+ cells from peripheral blood can reproduce bone marrow molecular profile in myelodysplastic syndromes.

Am. J. Hematol. Jun 2018, 93 (6) E152-E154. Epub 10 Apr 2018More information
Hurtado AM, Luengo-Gil G, Chen-Liang TH, Amaral F, Batta K, Palomo L, Lumbreras E, Przychodzen B, Caparros E, Amigo ML, Dıez-Campelo M, Zamora L, Salido Fierrez EJ, Maciejewski JP, Ortuño FJ, Vicente V, Del Canizo M, Sole F, Ferrer-Marin F, Wiseman DH, Jerez A

Transcriptomic rationale for synthetic lethality-targeting ERCC1 and CDKN1A in chronic myelomonocytic leukaemia.

Br. J. Haematol. 24 May 2018, . Epub 24 May 2018
Despite the absence of mutations in the DNA repair machinery in myeloid malignancies, the advent of high-throughput sequencing and discovery of splicing and epigenetics defects in chronic myelomonocytic leukaemia (CMML) prompted us to revisit a pathogenic role for genes involved in DNA damage response. We screened for misregulated DNA repair genes by enhanced RNA-sequencing on bone marrow from a discovery cohort of 27 CMML patients and 9 controls. We validated 4 differentially expressed candidates in CMML CD34
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Xicoy B, Triguero A, Such E, García O, Jiménez MJ, Arnán M, Bernal T, Diaz-Beya M, Valcárcel D, Pedro C, Ramos F, Amigo ML, Collado R, Palomo L, Ardanaz MT, Cedena MT, Grau J, Zamora L, Sanz G

The division of chronic myelomonocytic leukemia (CMML)-1 into CMML-0 and CMML-1 according to 2016 World Health Organization (WHO) classification has no impact in outcome in a large series of patients from the Spanish group of MDS.

Leuk. Res. 9 May 2018, 70 34-36. Epub 9 May 2018More information
Cabezón M, Bargay J, Xicoy B, García O, Borrás J, Tormo M, Marcé S, Pedro C, Valcárcel D, Jiménez MJ, Guàrdia R, Palomo L, Brunet S, Vall-Llovera F, Garcia A, Feliu E, Zamora L

Impact of mutational studies on the diagnosis and the outcome of high-risk myelodysplastic syndromes and secondary acute myeloid leukemia patients treated with 5-azacytidine.

Oncotarget 10 Apr 2018, 9 (27) 19342-19355. Epub 10 Apr 2018
Myelodysplastic syndromes (MDS) are stem cell disorders caused by various gene abnormalities. We performed targeted deep sequencing in 39 patients with high-risk MDS and secondary acute myeloid leukemia (sAML) at diagnosis and follow-up (response and/or relapse), with the aim to define their mutational status, to establish if specific mutations are biomarkers of response to 5-azacytidine (AZA) and/or may have impact on survival. Overall, 95% of patients harbored at least one mutation.
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Palomo L, Malinverni R, Cabezón M, Xicoy B, Arnan M, Coll R, Pomares H, García O, Fuster-Tormo F, Grau J, Feliu E, Solé F, Buschbeck M, Zamora L

DNA methylation profile in chronic myelomonocytic leukemia associates with distinct clinical, biological and genetic features.

Epigenetics 2018, 13 (1) 8-18. Epub 6 Feb 2018
Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions. Differential methylation analysis between patients and controls allowed us to identify abnormalities in DNA methylation, including hypermethylation of specific genes and large genome regions with aberrant DNA methylation. Unsupervised hierarchical cluster analysis identified two main clusters that associated with the clinical, biological, and genetic features of patients. Group 1 was enriched in patients with adverse clinical and biological characteristics and poorer overall and progression-free survival. In addition, significant differences in DNA methylation were observed between patients with low risk and intermediate/high risk karyotypes and between TET2 mutant and wild type patients. Taken together, our results demonstrate that altered DNA methylation patterns reflect the CMML disease state and allow to identify patient groups with distinct clinical features.
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Ribera J, Zamora L, Morgades M, Mallo M, Solanes N, Batlle M, Vives S, Granada I, Juncà J, Malinverni R, Genescà E, Guàrdia R, Mercadal S, Escoda L, Martinez-Lopez J, Tormo M, Esteve J, Pratcorona M, Martinez-Losada C, Solé F, Feliu E, Ribera JM

Copy number profiling of adult relapsed B-cell precursor acute lymphoblastic leukemia reveals potential leukemia progression mechanisms.

Genes Chromosomes Cancer Nov 2017, 56 (11) 810-820. Epub 26 Aug 2017
The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal despite new therapeutic approaches. Previous studies analyzing relapse samples have shown a high degree of heterogeneity regarding gene alterations without an evident relapse signature. Bone marrow or peripheral blood samples from 31 adult B-cell precursor ALL patients at first relapse, and 21 paired diagnostic samples were analyzed by multiplex ligation probe-dependent amplification (MLPA). Nineteen paired diagnostic and relapse samples of these 21 patients were also analyzed by SNP arrays. A trend to acquire homozygous CDKN2A/B deletions and a significant increase in the number of copy number alterations (CNA) was observed from diagnosis to first relapse. Evolution from an ancestral clone was the main pattern of clonal evolution. Relapse samples were extremely heterogeneous regarding CNA frequencies. However, CDKN2A/B, PAX5, ETV6, ATM, IKZF1, VPREB1, and TP53 deletions and duplications of 1q, 8q, 17q, 21, X/Y PAR1, and Xp were frequently detected at relapse. Duplications of genes involved in cell proliferation, drug resistance and stem cell homeostasis regulation, as well as deletions of KDM6A and STAG2 genes emerged as specific alterations at relapse. Genomics of relapsed adult B-cell precursor ALL is highly heterogeneous, although some recurrent lesions involved in essential pathways deregulation were frequently observed. Selective and simultaneous targeting of these deregulated pathways may improve the results of current salvage therapies.
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Palomo L, Fuster-Tormo F, Alvira D, Ademà V, Armengol MP, Gómez-Marzo P, de Haro N, Mallo M, Xicoy B, Zamora L, Solé F

Inspecting Targeted Deep Sequencing of Whole Genome Amplified DNA Versus Fresh DNA for Somatic Mutation Detection: A Genetic Study in Myelodysplastic Syndrome Patients.

Biopreserv Biobank Aug 2017, 15 (4) 360-365. Epub 6 Jun 2017
Whole genome amplification (WGA) has become an invaluable method for preserving limited samples of precious stock material and has been used during the past years as an alternative tool to increase the amount of DNA before library preparation for next-generation sequencing. Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by presenting somatic mutations in several myeloid-related genes. In this work, targeted deep sequencing has been performed on four paired fresh DNA and WGA DNA samples from bone marrow of MDS patients, to assess the feasibility of using WGA DNA for detecting somatic mutations. The results of this study highlighted that, in general, the sequencing and alignment statistics of fresh DNA and WGA DNA samples were similar. However, after variant calling and when considering variants detected at all frequencies, there was a high level of discordance between fresh DNA and WGA DNA (overall, a higher number of variants was detected in WGA DNA). After proper filtering, a total of three somatic mutations were detected in the cohort. All somatic mutations detected in fresh DNA were also identified in WGA DNA and validated by whole exome sequencing.
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Montoro J, Robledo C, Zamora L, Valcárcel D, Ramos F

Calreticulin mutations are exceedingly rare in patients with myelodysplastic syndromes with myelofibrosis.

Ann. Hematol. Feb 2017, 96 (2) 317-318. Epub 12 Oct 2016More information
Ribera J, Zamora L, García O, Hernández-Rivas JM, Genescà E, Ribera JM

[Copy number alterations in adult patients with mature B acute lymphoblastic leukemia treated with specific immunochemotherapy].

Med Clin (Barc) 2 Dec 2016, 147 (11) 488-491. Epub 27 Oct 2016
Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL.
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