Browsing by Subject "Leukemia"

Now showing 1 - 9 of 9
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    Anti-leukemic activity of Brassica-derived bioactive compounds in HL-60 myeloid leukemia cells
    (MDPI, 2022-11-02) Núñez-Sánchez, María Ángeles; Martínez-Sánchez, María Antonia; Verdejo-Sánchez, Marina; García-Ibáñez, Paula; Oliva Bolarín, Alba; Ramos-Molina, Bruno; Moreno, Diego A.; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
    Acute myeloid leukemia (AML) is a cancer of the myeloid blood cells mainly treated with chemotherapy for cancer remission, but this non-selective treatment also induces numerous side effects. Investigations with bioactive compounds from plant-derived foods against cancer have increased in the last years because there is an urgent need to search for new anti-leukemic agents possessing higher efficacy and selectivity for AML cells and fewer negative side effects. In this study, we analyzed the anti-leukemic activity of several phytochemicals that are representative of the major classes of compounds present in cruciferous foods (glucosinolates, isothiocyanates, hydroxycinnamic acids, flavonols, and anthocyanins) in the human acute myeloid leukemia cell line HL-60. Our results revealed that among the different Brassica-derived compounds assayed, sulforaphane (SFN) (an aliphatic isothiocyanate) showed the most potent anti-leukemic activity with an IC50 value of 6 µM in dose-response MTT assays after 48 h of treatment. On the other hand, chlorogenic acid (a hydroxycinnamic acid) and cyanidin-3-glucoside (an anthocyanin) also displayed anti-leukemic potential, with IC50 values of 7 µM and 17 µM after 48 h of incubation, respectively. Importantly, these compounds did not show significant cell toxicity in macrophages-like differentiated cells at 10 and 25 µM, indicating that their cytotoxic effects were specific to AML cancer cells. Finally, we found that these three compounds were able to induce the NRF2/KEAP1 signaling pathway in a dose-dependent manner, highlighting SFN as the most potent NRF2 activator. Overall, the present evidence shed light on the potential for using foods and ingredients rich in anticancer bioactive phytochemicals from Brassica spp.
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    Meiosis in hematological malignancies. In situ cytogenetic morphology
    (Murcia : F. Hernández, 1996) Logothetou-Rella, H.
    This is the first study on the in situ cytogenetic morphology and analysis of malignant bone marrow cells, growing attached on a culture vessel surface. It was documented that bone marrow cells, in different types of hematological malignancies, divide by meiosis giving rise to a non-repetitive aneuploidy. Male and female gametes are formed by meiosis and fertilization occurs in a life cycle of: Fertilization Meiosis Gametes - Embryo - Gametes Immature and mature somatic oocytes were evidenced by prophase stages of the first and diploid or hypodiploid or haploid metaphases identical to those of the second human, ovarian oocytic meiotic division, showing (o>r N X Y s~ex chromosomes in female or male patients respectively. Nuclear vlimata were the male gametes showing a condensed head with tail morphology. Metaphases of nuclear vlimata were aneuploid, keeping the head with tail shape, carrying chromosomes identical to those of human spermatogonia. Somatic metaphases identical to those of human spermatocytes in meiosis I1 and spermatogonia were demonstrated. The process of fertilization was documented by nuclear vlima invasion into host cell metaphases, by metaphases of fertilized oocyte showing both the female chromosome <) and hybrid metaphases of oocytic with somatic chromosomes. Meiosis was characterized by nuclear extrusion of chromosomes, meiotic, condensed chromosomes, nuclear vlimata, metaphase and nuclear fusion, hybrid metaphases, nuclear budding, nuclear conglomerates, nuclear bridges, chromosomal fusion substance, transfer of chromosomes and non-repetitive aneuploidy. Meiotic, Double Minute, ring and minute chromosomes extruded by nuclei were loaded with glycoproteins, glycosaminoglycans and calciumactivated neutral proteinase, distinguishing them from mitotic chromosomes. The main characteristic events of meiosis, observed in malignant bone marrow cells, were also demonstrated in fungal and rat testicular cells, known to divide by meiosis.
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    Natural killer cell malignancies: clinicopathologic and molecular features
    (Murcia : F. Hernández, 2002) Siu, L.L.P.; Chan, John K.C.; Kwong, Y.L.
    Malignancies of natural killer (NK) cells h ave increasingly been recognized as distinct clinicopathological entities. The tumor cells are characterized by an immunophenotype of CD2+, surface CD3-, cytoplasmic CD3e+, and CD56+. The T cell receptor gene is in germline configuration, and a consistent association with Epstein-Barr virus is demonstrable. Pa t h o l o g i c a l l y, the tumor cells show variable cytological appearances, with frequent angioinvasion and angiocentricity associated with zonal necrosis. Clinically, most cases affect the nasal cavity or other parts of the upper aerodigestive tract, and are referred to as nasal NK cell lymphoma. A minority involve extranasal sites such as the skin, gastrointestinal tract and testis, and are often referred to as ex t r a n a s a l NK cell lymphoma. A particularly aggressive form presents fulminantly as disseminated disease, sometimes with a leukemic phase, and is referred to as aggressive NK cell lymphoma/leukemia. Cytogenetic and molecular analysis have shown DNA losses at chromosomes 6q, 11q, 13q and 17p to be recurrent aberrations in NK cell malignancies. Frequent DNA gains are also found in chromosomes 1p, 6p, 11q, 12q, 17q, 19p, 20q, and Xp. These regions of DNA losses and gains should be targets for further inve s t i gation in order to understand the molecular pathogenesis of this lymphoma. Finally, optimal treatment modalities need to be determined, as all subtypes of NK cell malignancies are associated with a poor prognosis.
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    NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy
    (Cell Press, 2023-12-19) Hurtado-Navarro, Laura; Cuenca-Zamora, Ernesto J; Zamora, Lurdes; Bellosillo, Beatriz; Such, Esperanza; Soler-Espejo, Eva; Martínez-Banaclocha, Helios; Hernández-Rivas, Jesus M.; Marco-Ayala, Javier; Martínez-Alarcón, Laura; Linares-Latorre, Lola; García-Ávila, Sara; Amat-Martínez, Paula; González, Teresa; Arnan, Monserrat; Pomares-Marín, Helena; Carreño-Tarragona, Gonzalo; Chen-Liang, Tzu Hua; Herranz, Maria T.; García-Palenciano, Carlos; Morales, María Luz; Jerez, Andrés; Lozano, Maria L.; Teruel-Montoya, Raul; Ferrer-Marín, Francisca; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cells proliferation and survival, and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1β release. Here we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1β release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibit NLRP3 inflammasome activation, reduce monocyte count, and improve the patient’s clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers.
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    Regulation mechanisms for the heterodimeric transcription factor, PEBP2lCBF
    (Murcia : F. Hernández, 1999) Bae, S.C.; Ito, Y.
    Members of the new PEBP2 (Polyomavirus Enhancer Binding Protein 2) family of heterodimeric transcriptional regulatory protein are composed of two subunits, a and B. One of the genes encoding the a subunit, AMLlIPEBP2aB, was identified at the breakpoints of various chromosome translocations, including t(8;21) and t(12;21) associated with acute myeloid leukemia and acute lymphoblastic leukemia, respectively. The gene encoding the B subunit (PEBP2flCBFB) was also shown to be the target of the inversion of chromosome 16, another chromosomal anomaly associated with acute myeloid leukemia. Targeted disruption of either the AmlllPebp2aB or PebpZflICbfb gene resulted in strikingly similar phenotypes such as lack of definitive hematopoiesis of the fetal liver and accompanying hemorrhage of the central nervous system. These observations suggest that both a and l3 subunits of PEBP2 are indispensable for its in vivo function. However, the heterodimerization of the a and B subunit does not seem to occur readily suggesting that their capacity to associate might be an important rate limiting step in PEBP2 site-dependent transcription regulation. In this review, we concentrate on the possible regulatory mechanisms of PEBP2 activity in relation to leukemogenesis.
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    Role of WNT signaling in normal and malignant hematopoiesis
    (Murcia : F. Hernández, 2006) Khan, N.I.; Bendall, L.
    The WNT pathway is a powerful signaling pathway that plays a crucial role in cell fate determination, survival, proliferation and movement in variety of tissues. Abnormalities in the WNT signaling pathway have been implicated in a number of diseases, most notably cancer. Recent exciting evidence suggests that WNT signaling also plays an important role in hematopoietic stem cell self-renewal and progenitor development. In this review we discuss current state of knowledge on WNT signaling in hematopoiesis and extend our focus on aberrant WNT signaling in hematological malignancies.
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    SDF-1 and CXCR4 in normal and malignant hematopoiesis
    (Murcia : F. Hernández, 2004) Juarez, J.; Bendall, L.
    Over recent years it has become apparent that the chemokine SDF-1 and its receptor CXCR4 play pivotal roles in normal hematopoiesis. They are essential for the normal ontogeny of hematopoiesis during embryogenesis and continue to play a key role in retaining hematopoietic progenitors within the bone marrow microenvironment in the adult. As a result of this role disruption of SDF-1/CXCR4 interactions results in mobilization of hematopoietic progenitors and standard mobilization protocols disrupt this axis. Similarly SDF-1/CXCR4 interactions are required for homing and engraftment of hematopoietic stem cells during transplantation. SDF-1 regulates the localisation of leukemic cells and like their normal counterparts most leukemic cells respond to SDF-1 with increased adhesion, survival and proliferation. However in some instances leukemic cell responses to SDF-1 can be disregulated, the impact of which on the progression of disease in not known. In this review we discuss the pleiotropic roles of SDF-1/CXCR4 interactions in human hematopoietic stem cell ontogeny, bone marrow homing and engraftment, mobilization and how these interactions impact on malignant hematopoiesis.
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    Thrombocytopenia in leukemia: Pathogenesis and prognosis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Shahrabi, Saeid; Maleki Behzad, Masumeh; Jaseb, Kaveh; Saki, Najmaldin
    Leukemias, a heterogeneous group of hematological disorders, are characterized by ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells. Thrombocytopenia is a common problem among leukemia types that can lead to hemorrhagic complications in patients. The purpose of this review article is to identify the conditions associated with the incidence of thrombocytopenia in leukemias. It can be stated that although translocations have been considered responsible for this complication in many studies, other factors such as bone marrow failure, genes polymorphism, a mutation in some transcription factors, and the adverse effects of treatment could be associated with pathogenesis and poor prognosis of thrombocytopenia in leukemias. Considering the importance of thrombocytopenia in leukemias, it is hoped that the recognition of risk factors increasing the incidence of this complication in leukemic patients would be useful for prevention and treatment of this disorder.
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    Ultrastructural computerized morphometry of platelets in chronic myelogenous leukemia making use of ultra-thin sections and freeze-fracture procedure a preliminary approach
    (Murcia : F. Hernández, 1988) Bianciardi, G.; Battistelli, S.; Toti, P.; Vallesi, G.; Weber, G.
    Biochemical and morphological data have shown that the circulating platelets are deeply altered in patients with chronic mielogenous leukemia. In this report we describe the results of ultrastructural morphometry performed by means of a computerized device of the platelet shape (ultra-thin sectioned platelets) and of the platelet plasma-membrane (freezefractured platelets). Platelets appeared deeply modified: reduced mean platelet area and perimeter, increased surface density of the openings of the surface connected canalicular system, abnormal features of the platelet cytoplasm and some aspects of platelets joined together even if with heterogeneity in these findings did appear from patient to patient.