Publicació científica

S'han trobat 197 publicacions amb els criteris indicats.
Genescà E, Morgades M, González-Gil C, Fuster-Tormo F, Haferlach C, Meggendorfer M, Montesinos P, Barba P, Gil C, Coll R, Moreno MJ, Martínez-Carballeira D, García-Cadenas I, Vives S, Ribera J, González-Campos J, Díaz-Beya M, Mercadal S, Artola MT, Cladera A, Tormo M, Bermúdez A, Vall-Llovera F, Martínez-Sánchez P, Amigo ML, Monsalvo S, Novo A, Cervera M, García-Guiñon A, Ciudad J, Cervera J, Hernández-Rivas JM, Granada I, Haferlach T, Orfao A, Solé F, Ribera JM

Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL).

Leuk Res 8 Jun 2021, 109 106612. Epub 8 Jun 2021
The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.
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Celia González-Gil, Jordi Ribera, Josep Maria Ribera, Eulàlia Genescà

The Yin and Yang-Like Clinical Implications of the CDKN2A/ARF/CDKN2B Gene Cluster in Acute Lymphoblastic Leukemia

Genes 2021, 12, 79. 9 Gen 2021, .
Acute lymphoblastic leukemia (ALL) is a malignant clonal expansion of lymphoid hematopoietic precursors that exhibit developmental arrest at varying stages of differentiation. Similar to what occurs in solid cancers, transformation of normal hematopoietic precursors is governed by a multistep oncogenic process that drives initiation, clonal expansion and metastasis. In this process, alterations in genes encoding proteins that govern processes such as cell proliferation, differentiation, and growth provide us with some of the clearest mechanistic insights into how and why cancer arises. In such a scenario, deletions in the 9p21.3 cluster involving CDKN2A/ARF/CDKN2B genes arise as one of the oncogenic hallmarks of ALL. Deletions in this region are the most frequent structural alteration in T-cell acute lymphoblastic leukemia (T-ALL) and account for roughly 30% of copy number alterations found in B-cell-precursor acute lymphoblastic leukemia (BCP-ALL). Here, we review the literature concerning the involvement of the CDKN2A/B genes as a prognosis marker of good or bad response in the two ALL subtypes (BCP-ALL and T-ALL). We compare frequencies observed in studies performed on several ALL cohorts (adult and child), which mainly consider genetic data produced by genomic techniques. We also summarize what we have learned from mouse models designed to evaluate the functional involvement of the gene cluster in ALL development and in relapse/resistance to treatment. Finally, we examine the range of possibilities for targeting the abnormal function of the protein-coding genes of this cluster and their potential to act as anti-leukemic agents in patients.
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Sentís I, Gonzalez S, Genescà E, García-Hernández V, Muiños F, Gonzalez C, López-Arribillaga E, Gonzalez J, Fernandez-Ibarrondo L, Mularoni L, Espinosa L, Bellosillo B, Ribera JM, Bigas A, Gonzalez-Perez A, Lopez-Bigas N

The evolution of relapse of adult T cell acute lymphoblastic leukemia.

Genome Biol. 2020 Nov 23;21(1):284 20 Nov 2020, .
Background: Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent. A higher percentage of the adult patients relapse, compared to children. It is thus essential to study the mechanisms of relapse of adult T-ALL cases. Results: We profile whole-genome somatic mutations of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies and analyze their evolution upon treatment in comparison with 238 pediatric and young adult ALL cases. We compare the mutational processes and driver mutations active in primary and relapse adult T-ALLs with those of pediatric patients. A precise estimation of clock-like mutations in leukemic cells shows that the emergence of the relapse clone occurs several months before the diagnosis of the primary T-ALL. Specifically, through the doubling time of the leukemic population, we find that in at least 14 out of the 19 patients, the population of relapse leukemia present at the moment of diagnosis comprises more than one but fewer than 108 blasts. Using simulations, we show that in all patients the relapse appears to be driven by genetic mutations. Conclusions: The early appearance of a population of leukemic cells with genetic mechanisms of resistance across adult T-ALL cases constitutes a challenge for treatment. Improving early detection of the malignancy is thus key to prevent its relapse. Keywords: T-ALL, Adult acute lymphoblastic leukemia, T-ALL evolution under therapy, Evolution of leukemia relapse, ALL relapse
Comes M, Batlle M, Ribera JM

Treatment adapted to pregnancy in a patient with Burkitt lymphoma.

Med Clin (Barc) 12 Jun 2020, 154 (11) 470-471. Epub 20 Jul 2019Més informació
Sánchez R, Ribera J, Morgades M, Ayala R, Onecha E, Ruiz-Heredia Y, Juárez-Rufián A, de Nicolás R, Sánchez-Pina J, Vives S, Zamora L, Mercadal S, Coll R, Cervera M, García O, Ribera JM, Martínez-López J

A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics.

Blood Cancer J 24 Abr 2020, 10 (4) 43. Epub 24 Abr 2020
BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12-84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P ≤ 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15-60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1-like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL.
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Ribera JM, García O, Chapchap EC, Gil C, González-Campos J, Barba P, Amigo ML, Moreno MJ, Lavilla E, Alonso N, Bergua JM, Tormo M, Ribera J, Sierra M, Martínez-Carballeira D, Mercadal S, Hernández-Rivas JM, Vall-Llovera F, Genescà E, Cladera A, Novo A, Abella E, García-Cadenas I, Monteserín C, Bermúdez A, Piernas S, Montesinos P, López JL, García-Guiñón A, Serrano A, Martínez MP, Olivares M, López A, Serrano J

Treatment of Frail Older Adults and Elderly Patients With Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia: Results of a Prospective Trial With Minimal Chemotherapy.

Clin Lymphoma Myeloma Leuk 5 Abr 2020, . Epub 5 Abr 2020
The treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL).
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Sitges M, Boluda B, Garrido A, Morgades M, Granada I, Barragan E, Arnan M, Serrano J, Tormo M, Miguel Bergua J, Colorado M, Salamero O, Esteve J, Benavente C, Pérez-Encinas M, Coll R, Martí-Tutusaus JM, Brunet S, Sierra J, Ángel Sanz M, Montesinos P, Ribera JM, Vives S

Scute myeloid leukemia with inv(3)(q21q26.2)/t(3;3)(q21;q26.2). study of 61 patients treated with intensive protocols.

Eur. J. Haematol. 3 Abr 2020, . Epub 3 Abr 2020
Inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.
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Ribera JM, Morgades M, Montesinos P, Tormo M, Martínez-Carballeira D, González-Campos J, Gil C, Barba P, García-Boyero R, Coll R, Pedreño M, Ribera J, Mercadal S, Vives S, Novo A, Genescà E, Hernández-Rivas JM, Bergua J, Amigo ML, Vall-Llovera F, Martínez-Sánchez P, Calbacho M, García-Cadenas I, Garcia-Guiñon A, Sánchez-Sánchez MJ, Cervera M, Feliu E, Orfao A

A pediatric regimen for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: Results of the ALLRE08 PETHEMA trial.

Cancer Med Abr 2020, 9 (7) 2317-2329. Epub 5 Feb 2020
Pediatric-based or -inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL).
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Espasa A, Zamora L, Ribera JM

Granulocytic sarcoma: Study of two cases by high throughput sequencing.

Med Clin (Barc) 18 Mar 2020, . Epub 18 Mar 2020Més informació
Genescà E, Morgades M, Montesinos P, Barba P, Gil C, Guàrdia R, Moreno MJ, Martínez-Carballeira D, García-Cadenas I, Vives S, Ribera J, González-Campos J, González-Gil C, Zamora L, Ramírez JL, Díaz-Beya M, Mercadal S, Artola MT, Cladera A, Tormo M, Bermúdez A, Vall-Llovera F, Martínez P, Amigo ML, Monsalvo S, Novo A, Cervera M, García-Guiñon A, Juncà J, Ciudad J, Orfao A, Ribera JM

Unique clinico-biological, genetic and prognostic features of adult early T cell precursor acute lymphoblastic leukemia.

Haematologica 19 Set 2019, . Epub 19 Set 2019Més informació