Acute Lymphoblastic Leukemia (ALL)

  • Ribera Group
ICO - German Trias i Pujol

Josep Carreras Leukaemia Research Institute
Edifici IMPPC
Can Ruti Campus
Ctra de Can Ruti, Camí de les Escoles s/n
08916 Badalona, Barcelona, Spain

 

Directions

Summary

Our research is focused on Acute lymphoblastic Leukemia (ALL) disease, including B-cell precursor and T-precursor ALL. We want to resolve questions that require a full range of research from from basic to clinical. We aim to provide the physician with new tools, by using basic research data that will have an impact on healthcare, in order to improve survival rates in patients with this type of leukaemia.

Research

Acute Lymphoblastic Leukemia is still a non-curable neoplasia mainly in adult patients. The survival rates for ALL are much lower in adults than in children. The reasons for this survival difference lie largely in the higher frequency of poor prognosis subtypes of ALL in adults and a poorer tolerance of the treatment as age increases. Except for selected subgroups (i.e., Ph+ ALL), the current therapeutic protocols for ALL do not take into account the differences in the molecular background of the disease, and few new alternative therapies are only available in refractory or resistant ALL. Therefore, if we want to improve the survival of patients with ALL we first need to obtain detailed and relevant molecular information to enable doctors to accurately define the risk and decide on the treatment. Secondly, we need to have specific therapeutic alternatives available to apply to these new oncogenetic ALL subgroups.

Main Research Lines:

The current research of the group at the IJC Institute can be divided in two main areas:

1: Clinical research: Design and analysis of the results of the Spanish treatment protocols on adult ALL in the setting of the Spanish PETHEMA group (Programa Español de Tratamientos en Hematología).

2. Biologic and translational research: the ALL Group is currently evaluating the frequency and prognostic significance of new genetic markers in B-lineage ALL. The results of this study, which are in line with the results found by other ALL working groups, will be applied in the new therapeutic protocols in ALL of the PETHEMA group. Next, we will evaluate the prognosistic impact of methylation in specific genes with an important roles in leukemogenesis.

We are also interested in validating and identifying new prognosistic markers for T-ALL. In addition, we want to assess the anti-leukemic effect of the available drugs that specifically target these genes in an in vivo model. We also want to check if copy number alterations (CNAs) identified in other blood neoplasias such as; Acute Myeloblastic Leukaemia (AML), Non-Hodgkin Lymphoma (NHL) and Chronic Myeloid Leukaemia (CLL), or in solid cancers such as Melanoma and Breast Cancer, could also have an impact on T-ALL leukaemia. We expect that the results obtained, will be used to re-classify T-ALL patients into different oncogenetic subgroups according to the predicted treatment response and the specific target therapy to be applyied.

The identification of clonal heterogeneity in ALL at the time of diagnosis has introduced a high order of complexity to the disease. It is this clonal heterogeneity that is responsible for patient’s relapses, in which treatment has failed. Future projects in the group will be focused on the characterization of leukemic cells resistant to treatment using a genetic and functional approach.

Collaborations

People

Selected publications

Ribera JM, García O, Oriol A, Gil C, Montesinos P, Bernal T, González-Campos J, Lavilla E, Ribera J, Brunet S, Martínez MP, Tormo M, Genescà E, Barba P, Sarrà J, Monteserín MC, Soria B, Colorado M, Cladera A, García-Guiñón A, Calbacho M, Serrano A, Ortín X, Pedreño M, Amigo ML, Escoda L, Feliu E

Feasibility and results of subtype-oriented protocols in older adults and fit elderly patients with acute lymphoblastic leukemia: Results of three prospective parallel trials from the PETHEMA group.

Leuk. Res. 2 Des 2015, . Epub 2 Des 2015
The prognosis of acute lymphoblastic leukemia (ALL) is poor in older adults and elderly patients, and subtype-oriented prospective trials are scarce in these patients. We present the results of three prospective parallel subtype-oriented protocols in fit patients older than 55 years.
Més informació
Ribera J, Morgades M, Zamora L, Montesinos P, Gómez-Seguí I, Pratcorona M, Sarrà J, Guàrdia R, Nomdedeu J, Tormo M, Martínez-Lopez J, Hernández-Rivas JM, González-Campos J, Barba P, Escoda L, Genescà E, Solé F, Millá F, Feliu E, Ribera JM

Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols.

Cancer 1 Nov 2015, 121 (21) 3809-17. Epub 20 Jul 2015
Some copy number alterations (CNAs) have independent prognostic significance for adults with acute lymphoblastic leukemia (ALL).
Més informació
Ribera JM, Ferrer A, Ribera J, Genescà E

Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia.

Onco Targets Ther 2015, 8 1567-74. Epub 24 Jun 2015
The CD19 marker is expressed on the surface of normal and malignant immature or mature B-cells. On the other hand, immunotherapy involving T-cells is a promising modality of treatment for many neoplastic diseases including leukemias and lymphomas. The CD19/CD3-bispecific T-cell-engaging (BiTE(®)) monoclonal antibody blinatumomab can transiently engage cytotoxic T-cells to CD19+ target B-cells inducing serial perforin-mediated lysis. In the first clinical trial, blinatumomab showed efficacy in non-Hodgkin's lymphomas, but the most important trials have been conducted in relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and in ALL with minimal residual disease. Encouraging reports on the activity of blinatumomab in R/R Philadelphia chromosome-negative B-cell precursor ALL led to its approval by the US Food and Drug Administration on December 3, 2014 after an accelerated review process. This review focuses on the profile of blinatumomab and its activity in R/R ALL.
Més informació
Ribera JM, Ribera J, Genescà E

Treatment of adolescent and young adults with acute lymphoblastic leukemia.

Mediterr J Hematol Infect Dis 2014, 6 (1) e2014052. Epub 2 Jul 2014
The primary objective of this review was to update and discuss the current concepts and the results of the treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA). After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALL in the AYA population, the main retrospective comparative studies stating the superiority of pediatric over adult-based protocols were reviewed. The most important prospective studies in young adults using pediatric inspired or pediatric unmodified protocols were also reviewed emphasizing their feasibility at least up to the age of 40 yr and their promising results, with event-free survival rates of 60-65% or greater. Results of trials from pediatric groups have shown that the unfavourable prognosis of adolescents is no more adequate. The majority of the older adolescents with ALL can be cured with risk-adjusted and minimal residual disease-guided intensive chemotherapy, without stem cell transplantation. However, some specific subgroups, which are more frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like), deserve particular attention. In summary, the advances in treatment of ALL in adolescents have been translated to young adults, and that explains the significant improvement in survival of these patients in recent years.
Més informació
Genescà E, Ribera J, Ribera JM

[Acute lymphoblastic leukemia of T progenitors: From biology to clinics.]

Med Clin (Barc) 9 Mar 2015, 144 (5) 223-229. Epub 22 Mar 2014
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications.
Més informació
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Current projects

Comparison of next generation sequencing (NGS) and high sensitivity citometry to asses minimal residual disease (MRD) in childhood and adult acute lymphoblastic leukemia

Responsable:José María Ribera
Codi:PI14/01971
Financiadors:
Data d'inici:01/01/2015
Data de finalització:31/12/2017

Identification of copy number alterations as targets for available drugs involved in T-ALL leukemogenesis and prognosis

Responsable:Eulàlia Genesca
Codi:CELGENE T-ALL
Financiadors:
Data d'inici:01/01/2014
Data de finalització:31/12/2016

Grup de Recerca Emergent: Grup de Recerca d'estudi de les neoplàsies hematològiques del IJC-Campus Trias i Pujol

Responsable:Francesc Solé
Codi:2014SGR225
Financiadors:
Data d'inici:01/01/2015
Data de finalització:31/12/2017

Exploring Mechanisms of Resistance in Adult and Pediatric T-Acute Lymphoblastic Leukemia;(A.Bigas,IMIM)&(J.M.Ribera-E.Genescà,IJC)

Responsable:José María Ribera
Codi:GC16173697BIGA
Financiadors:
Data d'inici:01/11/2016
Data de finalització:31/10/2021

Previous projects

Study of the frequency and prognostic significance of Copy Number Alterations and CpG island methylation status in adult B-precursor Acute Lymphoblastic Leukemia patients enrolled in risk-adapted protocols of the Spanish PETHEMA Group

Responsable:José María Ribera
Codi:RD12/0036/0829
Financiadors:
Data d'inici:01/01/2011
Data de finalització:30/06/2014