Immunotherapy in Pediatric Acute Leukemia: A Novel Magic Bullet or an Illusory Hope?

The last decade became the renaissance for investigating and exploring the potential role of immunotherapy in pediatric acute leukemia (AL). It is beyond question that there is an interaction between innate immune system and hematological malignancy. Leukemia cells inhibit the host immune response according to multiple mechanisms, but exploiting the innate immune system mechanisms can overcome the resistance to the conventional treatment. What is the role of immunotherapy in pediatric AL treatment? Does it have the potential to substitute or combine the standard chemotherapy? What is the best possible timing to take advantage of immune interventions? This review is considered to follow through the possible treatment options including their foundation, strong and weak points, but also information about possible implementation into the clinical practice

Effects of Noonan Syndrome-Germline Mutations on Mitochondria and Energy Metabolism

Noonan syndrome (NS) and related Noonan syndrome with multiple lentigines (NSML) contribute to the pathogenesis of human diseases in the RASopathy family. This family of genetic disorders constitute one of the largest groups of developmental disorders with variable penetrance and severity, associated with distinctive congenital disabilities, including facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition. NS was first clinically described decades ago, and several genes have since been identified, providing a molecular foundation to understand their physiopathology and identify targets for therapeutic strategies. These genes encode proteins that participate in, or regulate, RAS/MAPK signalling. The RAS pathway regulates cellular metabolism by controlling mitochondrial homeostasis, dynamics, and energy production; however, little is known about the role of mitochondrial metabolism in NS and NSML. This manuscript comprehensively reviews the most frequently mutated genes responsible for NS and NSML, covering their role in the current knowledge of cellular signalling pathways, and focuses on the pathophysiological outcomes on mitochondria and energy metabolism

Posterior reversible encephalopathy syndrome (PRES) induced by intrathecal methotrexate administration in a patient with acute lymphoblastic leukaemia

A patient with B-cell precursor acute lymphoblastic leukaemia was diagnosed with posterior reversible encephalopathy syndrome (PRES) after an intrathecal administration of methotrexate during induction chemotherapy. PRES presented with headache, epilepsy, unconsciousness, blurred vision, hypertension, and vomiting. Also, characteristic lesions of the central nervous system were revealed by magnetic resonance imaging of the head, especially in the white matter of the posterior lobes

Acute Myeloid Leukemia in Pediatric Patients: A Review About Current Diagnostic and Treatment Approaches

Acute leukemia is the most common childhood malignancy, accounting for almost 35% of all childhood cancers. Acute myeloid leukemia (AML) represents 15–20% of pediatric acute leukemia. Majority of AML cases appear de novo, however a minority of cases can present as a secondary malignancy. AML is a highly heterogeneous disease and its diagnosis involves a combination of diagnostic analyses including morphology, immunophenotyping, cytochemistry, and leukemic blasts derived from peripheral blood or bone marrow demonstrating cytogenic and molecular characteristics. Through the identification of recurrent genetic mutations, it has been made possible to refine individual prognosis and guide therapeutic management. The current survival rate of children with AML is approximately 70%. The standard therapeutic regimen is a combination of cytarabine- and anthracycline-based regimens with allogenic stem cell transplantation in appropriate patients. Relapse in pediatric patients suffering from AML occurs in approximately 30% of cases, whereas death occurs in 5–10% of patients as a result of disease complications or chemotherapeutic side effects. In understanding the genetic basis of AML, targeted therapies will have the ability to reduce treatment-related morbidity and mortality. Here, we provide a comprehensive review of AML, its biology, diagnosis and therapeutic management in pediatric patients

Fronteras y zonas fronterizas en América Latina y el Caribe

Les presentamos el Dossier del volumen sexto de la revista “Anuario Latinoamericano – Ciencias Políticas y Relaciones Internacionales” dedicado al estudio del tema de las fronteras en América Latina. En los tiempos presentes el tema del funcionamiento de las fronteras y zonas fronterizas tiene gran importancia tanto desde la perspectiva de la política interna como de la política internacional de los Estados y es foco de atención de los académicos de Europa y América Latina.Les presentamos el Dossier del volumen sexto de la revista “Anuario Latinoamericano – Ciencias Políticas y Relaciones Internacionales” dedicado al estudio del tema de las fronteras en América Latina. En los tiempos presentes el tema del funcionamiento de las fronteras y zonas fronterizas tiene gran importancia tanto desde la perspectiva de la política interna como de la política internacional de los Estados y es foco de atención de los académicos de Europa y América Latina

Comparison of treatment results in children with non-high risk acute lymphoblastic leukaemia treated according to ALL-BFM 90 and ALL-IC BFM 2002 regimens – single centre preliminary experience

BackgroundAcute lymphoblastic leukaemia (ALL) represents about 30% of cancer in children and thus is the most common childhood malignancy. Despite the great progress, further improvement of treatment results remains an important problem.AimA comparison of the results of standard risk and intermediate risk group regimens ALL-BFM 90 and ALL IC-BFM 2002 was the subject of our study.Materials/MethodsA retrospective analysis of 41 (18 males and 23 females) children aged 2–15 years (median: 6 years) diagnosed from 25.01.1994 to 9.04.1997 and treated according to ALL-BFM 90 (group A), and 44 (22 males and 22 females) children aged 0-18 years (median: 7 years) diagnosed from 12.10.2002 to 31.12.2005 and treated according to ALL IC BFM-2002 regimen (group B) was performed. For statistical evaluation Kaplan–Meier methods and the log-rank test were used.ResultsRemission on time (day +33) was achieved in 39/41 (94%) children from group A and in 43/44 (98%) children from group B (p=0.07). The average day of achieving remission was 49 (range: 28–109; median: 46) in group A and 39 (range: 31–71; median: 35) in group B (

Zaburzenia genetyczne w ostrej białaczce limfoblastycznej u dzieci i ich wykorzystanie w praktyce klinicznej

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood anda heterogeneous disorder characterized by excessive proliferation and differentiation block. Thebasis of this process is formed by genetic aberrations: a large spectrum of mutations andrearrangements affect essential cellular transduction pathways, genes assuring proper courseof the hematopoiesis, oncogenes, tumor suppressors and apoptosis regulators. Application ofnovel molecular technologies and research methods allow to understanding the biology ofleukemogenesis, identified new diagnostic and prognostic markers based on gene expressionand used to stratify patients and to individualize therapy and improve the determination ofrisk factors in each age group. This review presents the current status of knowledge on geneticaberrations in both pediatric B-cell precursor and T-cell ALL.Ostra białaczka limfoblastyczna (ALL) jest najczęstszym nowotworem układu krwiotwórczegowieku dziecięcego oraz heteregenną chorobą charakteryzującą się nadmierną proliferacjąi zahamowaniem różnicowania. U podstaw ALL leżą zaburzenia genetyczne o charakterzeróżnego rodzaju mutacji i rearanżacji w obrębie kluczowych sygnałów przekaźnictwa komórkowego,genów warunkujących prawidłowy przebieg hematopoezy, onkogenów, genów supresorowychi regulatorów apoptozy. Zastosowanie nowych technologii molekularnych i metod badawczychpozwala na coraz dokładniejsze poznanie biologicznego podłoża leukemogenezy, poszukiwanienowych markerów o znaczeniu diagnostycznym i prognostycznym, o wartościprzydatnej w reklasyfikacji pacjentów do grup ryzyka, a także na odkrywanie nowych cząstekdocelowych dla zindywidualizowanych terapii. W prezentowanej pracy przedstawiono obecnypoziom wiedzy na temat zaburzeń genetycznych występujących w dziecięcej ALL

Zespół tylnej odwracalnej encefalopatii wyindukowany dokanałowym podaniem metotreksatu u pacjenta z ostrą białaczką limfoblastyczną

U pacjenta z ostrą białaczką limfoblastyczną o różnicowaniu B-common rozpoznano zespół tylnej odwracalnej encefalopatii (PRES, posterior reversible encephalopathy syndrome) po dokanałowym podaniu metotreksatu w trakcie chemioterapii indukcyjnej. Zespół PRES objawia się bólami głowy, padaczką, zaburzeniami świadomości, zaburzeniami widzenia, nadciśnieniem tętniczym oraz wymiotami. W badaniu rezonansu magnetycznego głowy widoczne są charakterystyczne zmiany w istocie białej mózgu, szczególnie w płatach tylnych

A child with a central nervous system relapse of a facial embryonal rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. There are two main types of RMS: embryonal and alveolar (having a worse prognosis). The treatment for childhood RMS is based on surgery, chemotherapy and radiation. In spite of very intensive therapy, 1/3 of patients suffer a relapse. The case report presents a child with facial embryonal RMS with an atypical central nervous system relapse; this, despite a comprehensive diagnostic process, was diagnosed during the autopsy

Regulation of Amino Acid Metabolism in Hematological Malignancies: Advances from Transcriptomics and Metabolomics

open access article STER Internationalisation of Doctoral Schools ProgrammeTumor cells use amino acids to rewire metabolic pathways to meet increased demands for energy, reducing equivalents, and cellular biosynthesis. Aside acting as building blocks for protein synthesis, amino acids also function as metabolic intermediates for ATP generation and redox homeostasis, as well as fueling biosynthetic pathways. Tumor-related metabolic changes infl uence every stage of the interaction between cells and their metabolites. Over the years, advancements in molecular methods such as transcriptomics and metabolomics have emerged to provide in-depth knowledge into the functions, interactions, and actions of molecules in cells of organisms. These technologies surfaced as methods that provide a more complete picture of disease pathophysiology, facilitating the elucidation of disease mechanisms and identify cation of potential biomarkers (metabolites) and targets (genes) respectively. Though Omics in cancer research have been explored in different concepts, however, employing these methods in amino acid metabolism in hematological cancers still requires attention. Therefore, this mini review discusses an up-to-date knowledge of principal regulators and their role in amino acid metabolism in hematological malignancies. In that perspective, we cover relevant fi ndings from transcriptomics and metabolomics, thereby constructing mechanistic insights associated with disease pathogenesis