Eduardo Anguita

Hospital Clínico San Carlos

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Ana Villegas

Hospital Clínico San Carlos

Joaquín Martínez‐López

Hospital Universitario 12 De Octubre

Paloma Ropero

Hospital Clínico San Carlos

Fernando A. González

New York Hospital Queens

Clara Bueno

Josep Carreras Leukaemia Research Institute

Pablo Menéndez

Josep Carreras Leukaemia Research Institute

Douglas R. Higgs

MRC Weatherall Institute of Molecular Medicine

Rosa Ayala

Hospital Universitario 12 De Octubre

Eva Barragán

Hospital Universitari i Politècnic La Fe

María Teresa Gómez‐Casares

Universidad de Las Palmas de Gran Canaria

Cooperative Institutions

Centro de Investigación Biomédica en Red de Cáncer

328

Instituto de Investigación Biomédica de Salamanca

248

Hospital Clínico San Carlos

140

Universidad Complutense de Madrid

122

Instituto de Investigación Sanitaria del Hospital Clínico San Carlos

107

Instituto de Salud Carlos III

106

Hospital Universitario Fundación Jiménez Díaz

Universitat de Barcelona

Hospital Universitario 12 De Octubre

Hospital General Universitario de Alicante Doctor Balmis

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Data-driven flow cytometry classification of blast differentiation in older patients with acute myeloid leukemia

Deleted Journal (2024)

Catia Simoes Carmen González François Vergez Audrey Sarry Sarah Bertoli

10.1016/j.bneo.2024.100027

Cite

Citations (0)

Lineage-Specific Transcriptional Regulation of GATA1 Is Dependent on Lineage-Specific Utilisation of Multiple Cis-Elements and Haematopoietic Transcription Factors.

Blood (2004)

Paresh Vyas Boris Guyot Verónica Valverde-Garduño Eduardo Anguita Isla Hamlett

GATA1

Chromatin immunoprecipitation

Transcription

GATA2

Locus control region

10.1182/blood.v104.11.1610.1610

Cite

Citations (0)

Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated immune recognition

Oncotarget (2017)

Aroa Baragaño Raneros Alfredo Minguela Ramón María Alvargonzález Rodríguez Enrique Colado Teresa Bernal

Acute myeloid leukemia (AML) is a disease with great morphological and genetic heterogeneity, which complicates its prognosis and treatment. The hypomethylating agents azacitidine (Vidaza®, AZA) and decitabine (Dacogen®, DAC) have been approved for the treatment of AML patients, but their mechanisms of action are poorly understood. Natural killer (NK) cells play an important role in the recognition of AML blasts through the interaction of the activating NKG2D receptor with its ligands (NKG2DL: MICA/B and ULBPs1-3). However, soluble NKG2DL (sNKG2DL) can be released from the cell surface, impairing immune recognition. Here, we examined whether hypomethylating agents modulate the release of sNKG2DL from AML cells. Results demonstrated that AZA- and DAC-treated AML cells reduce the release of sNKG2DL, preventing downregulation of NKG2D receptor on the cell surface and promoting immune recognition mediated by NKG2D-NKG2DL engagement. We show that the shedding of MICA, MICB and ULBP2 is inhibited by the increased expression of TIMP3, an ADAM17 inhibitor, after DAC treatment. The TIMP3 gene is highly methylated in AML cells lines and in AML patients (25.5%), in which it is significantly associated with an adverse cytogenetic prognosis of the disease. Overall, TIMP3 could be a target of the demethylating treatments in AML patients, leading to a decrease in MICA, MICB and ULBP2 shedding and the enhancement of the lytic activity of NK cells through the immune recognition mediated by the NKG2D receptor.

NKG2D

Azacitidine

Decitabine

Demethylating agent

10.18632/oncotarget.16657

Cite

Citations (44)

Occurrence of BCR-ABL rearrangement in a Philadelphia chromosome-negative patient with 5q and 13q deletions and myeloproliferative syndrome

Cancer Genetics and Cytogenetics (1998)

Ana Villegas Eduardo Anguita Fernando A. González Maria Teresa Ferrò Carlos Román

breakpoint cluster region

Philadelphia chromosome

Southern blot

Nondisjunction

Gene rearrangement

10.1016/s0165-4608(97)00003-4

Cite

Citations (15)

Antología de poesía chilena nueva (1935)

LOM Ediciones eBooks (2001)

Eduardo Anguita Volodia Teitelboim

Source

Cite

Citations (1)

The Multi-Kinase Inhibitor EC-70124 Is a Promising Candidate for the Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia

Cancers (2022)

Belén López‐Millán Paula Costales Francisco Gutiérrez‐Agüera Rafael Díaz de la Guardia Heleia Roca-Ho

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Patients with AML harboring a constitutively active internal tandem duplication mutation (ITDMUT) in the FMS-like kinase tyrosine kinase (FLT3) receptor generally have a poor prognosis. Several tyrosine kinase/FLT3 inhibitors have been developed and tested clinically, but very few (midostaurin and gilteritinib) have thus far been FDA/EMA-approved for patients with newly diagnosed or relapse/refractory FLT3-ITDMUT AML. Disappointingly, clinical responses are commonly partial or not durable, highlighting the need for new molecules targeting FLT3-ITDMUT AML. Here, we tested EC-70124, a hybrid indolocarbazole analog from the same chemical space as midostaurin with a potent and selective inhibitory effect on FLT3. In vitro, EC-70124 exerted a robust and specific antileukemia activity against FLT3-ITDMUT AML primary cells and cell lines with respect to cytotoxicity, CFU capacity, apoptosis and cell cycle while sparing healthy hematopoietic (stem/progenitor) cells. We also analyzed its efficacy in vivo as monotherapy using two different xenograft models: an aggressive and systemic model based on MOLM-13 cells and a patient-derived xenograft model. Orally disposable EC-70124 exerted a potent inhibitory effect on the growth of FLT3-ITDMUT AML cells, delaying disease progression and debulking the leukemia. Collectively, our findings show that EC-70124 is a promising and safe agent for the treatment of AML with FLT3-ITDMUT.

Midostaurin

CD135

Debulking

10.3390/cancers14061593

Cite

Citations (3)

C3G, through its GEF activity, induces megakaryocytic differentiation and proplatelet formation

Cell Communication and Signaling (2018)

Sara Ortiz-Rivero Cristina Baquero Luis Hernández-Cano Juan José Roldán‐Etcheverry Sara Gutiérrez-Herrero

Megakaryopoiesis allows platelet formation, which is necessary for coagulation, also playing an important role in different pathologies. However, this process remains to be fully characterized. C3G, an activator of Rap1 GTPases, is involved in platelet activation and regulates several differentiation processes.We evaluated C3G function in megakaryopoiesis using transgenic mouse models where C3G and C3GΔCat (mutant lacking the GEF domain) transgenes are expressed exclusively in megakaryocytes and platelets. In addition, we used different clones of K562, HEL and DAMI cell lines with overexpression or silencing of C3G or GATA-1.We found that C3G participates in the differentiation of immature hematopoietic cells to megakaryocytes. Accordingly, bone marrow cells from transgenic C3G, but not those from transgenic C3GΔCat mice, showed increased expression of the differentiation markers CD41 and CD61, upon thrombopoietin treatment. Furthermore, C3G overexpression increased the number of CD41+ megakaryocytes with high DNA content. These results are supported by data obtained in the different models of megakaryocytic cell lines. In addition, it was uncovered GATA-1 as a positive regulator of C3G expression. Moreover, C3G transgenic megakaryocytes from fresh bone marrow explants showed increased migration from the osteoblastic to the vascular niche and an enhanced ability to form proplatelets. Although the transgenic expression of C3G in platelets did not alter basal platelet counts, it did increase slightly those induced by TPO injection in vivo. Moreover, platelet C3G induced adipogenesis in the bone marrow under pathological conditions.All these data indicate that C3G plays a significant role in different steps of megakaryopoiesis, acting through a mechanism dependent on its GEF activity.

Thrombopoiesis

Megakaryocytopoiesis

10.1186/s12964-018-0311-5

Cite

Citations (18)

High incidence of the CD8/9 (+G) beta 0-thalassemia mutation in Spain.

PubMed (1998)

Ana Villegas Paloma Ropero Fernando A. González Edelmira Martí Eduardo Anguita

In Spain, as in other Mediterranean regions the most common beta-thalassemia mutations are due to point mutations in gene regions that are critical for production of mRNA, such as [IVS-I-nt1 (G-->A), IVS-I-nt6 (T-->C), IVS-I-nt110 (G-->A)] which interrupt normal RNA processing or nonsense mutations [CD39 (C-->T)] which interrupt the translation of mRNA. The frameshift mutation CD8/9 (+G) is a very common allele in Asian Indians but is rare in the Mediterranean regions in which isolated alleles with this mutation have been found in Israel, Greece, Portugal and Turkey.We performed a molecular analysis of 175 chromosomes corresponding to 233 beta-thalassemia patients (221 heterozygous, 10 homozygous and 2 compound heterozygous) who belong to 169 Spanish families. The study of beta-thalassemia was made by PCR-ARMS, the alpha genes by Southern blot, the phenotype of Hb Lepore by enzymatic amplification and the presence of -158 gamma G C-->T mutation by PCR and digestion with the restriction enzyme XmnL.Twenty of these 233 patients showed the beta-thalassemia mutation CD8/9 (+G) (17 were heterozygous, 2 homozygous and in one patient the mutation was associated with a structural variant Hb Lepore Boston).These data reveal the heterogeneity of beta-thalassemia in Spain and the relatively high frequency (8.6%) of the frameshift mutation CD8/9 (+G). It is surprising that homozygotes for beta zero-thalassemia due to this mutation with very high Hb F values (around 90%) present a phenotype of intermediate thalassemia.

Nonsense mutation

Compound heterozygosity

Beta thalassemia

Microcytosis

Source

Cite

Citations (6)

Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2

The EMBO Journal (2004)

Eduardo Anguita Jim R. Hughes Clare M. Heyworth Gerd A. Blobel W. G. Wood

10.1038/sj.emboj.7600274

Cite