6.2.3 Propiedades del concepto: relaciones complejas

Como ya hemos mencionado, las relaciones complejas son aquellas que se establecen entre conceptos de una jerarquía. Estas relaciones son las propiedades que definen y caracterizan un concepto y hacen posible diferenciarlo de los demás. Incluimos a continuación algunas de las sondas de conocimiento que nos ofrecieron información sobre dichas relaciones, junto con ejemplos de líneas de concordancia extraídas usando la combinación de la palabra leuk(a)emia + sonda de conocimiento.

Una de las primeras sondas a las que acudimos fue la palabra clave asociada diagnosis, que buscamos usando caracteres comodín, en la forma diagnos*, para dar cabida a la extracción de los usos verbales de la raíz. En las concordancias que extrajimos, encontramos información muy valiosa sobre los pruebas y criterios diagnósticos usados en la leucemia y otros aspectos relacionados, como la importancia de un adecuado diagnóstico para establecer el tratamiento correcto o las semejanzas diagnósticas entre varios tipos de leucemias. Ofrecemos a continuación algunas de las líneas de concordancia extraídas:

The diagnosis of acute leukemia requires the demonstration of leukemic cells in the bone marrow, peripheral blood, or extramedullary tissues.

Taking these data together, it can be stated that the use of anti-MPO McAbs may be of great value for the diagnosis and monitoring of acute leukemia and, along with lysozyme McAb, can provide useful information in the distinction of myeloid from monocytic leukemias and in the lineage assignment of apparently biphenotypic forms.

Smoldering AML refers to a syndrome in which the diagnostic features of acute leukemia are present, but the disease follows an indolent or subacute course.

Special histochemical stains should be performed on bone marrow specimens of all children with acute leukemia to confirm their diagnosis. The stains most commonly used include myeloperoxidase, PAS, Sudan Black B, and esterase.

However, various "lineage-specific" monoclonal antibodies that detect antigens on AML cells should be used at leukemia diagnosis, along with a battery of lineage-specific T- and B- lymphocyte markers to help distinguish AML from ALL and mixed lineage or biphenotypic or biclonal leukemias.

Hairy cell leukemia may be difficult to diagnose early because it symptoms are vague and resemble those of other illnesses.

Patients with established CNS leukemia at diagnosis require the use of intrathecal therapy followed by cranial irradiation.

Patients with CNS leukemia at diagnosis receive craniospinal irradiation at the beginning of Consolidation; those with testicular disease receive bilateral testicular irradiation during Consolidation.

Although the presence of central nervous system (CNS) leukemia at diagnosis (i.e., clinical neurologic features and/or leukemic cells in cerebral spinal fluid on cytocentrifuge preparation) is more common in childhood AML than in childhood acute lymphocytic leukemia (ALL), reduction in overall survival directly attributable to CNS involvement is presently less common in childhood AML.

Bone marrow aspiration evaluates the stem cells that mature into normal blood cells. The procedure is used to diagnose leukemia and to check the response to treatment.

Untreated adult acute myeloid leukemia (AML) is defined as newly diagnosed leukemia with no prior treatment.

How is leukemia diagnosed? To find the cause of a person's symptoms, the doctor asks about the patient's medical history and does a physical exam.

The differential diagnosis of LGL leukemia should be considered in two different contexts: diseases associated with CD56 expression and those associated with reactive LGL proliferation.

The diagnosis of chronic lymphocytic leukemia may provide a profound emotional response in patients, family members, and friends. Denial, depression, a feeling of hopelessness, and fear are normal and usual reactions. No one response is either expected or unexpected.

The report of an elevated white blood cell count is the most common clue that leads a physician to consider the diagnosis of chronic lymphocytic leukemia.

Diagnosis of leukemia requires blood tests and examination of the cells in the bone marrow, because early symptoms can mimic many other diseases including mononucleosis, anemia arising from other causes, tonsillitis, rheumatic conditions, meningitis, mumps and other kinds of cancer.

Although cytomorphology of the hematopoietic tissue had been exquisitely defined with the use of Romanowsky stains coupled with electron microscopy, the diagnosis of leukemia was, before 1945, a death sentence for want of effective therapy.

Diagnosis of leukemia is supported by findings of the medical history and examination, and examining blood under a microscope. Leukemia cells can also be detected and further classified with a bone marrow aspiration and/or biopsy.

Correct diagnosis of acute promyelocytic leukemia (APL) requires proof of the translocation (15;17)(q24;q11), which appears to be absolutely specific for this particular type of myeloid disorder.

El uso de treat* como sonda de conocimiento nos permitió extraer información sobre el tratamiento de diferentes tipos de leucemia, los efectos secundarios de algunos de estos tratamientos o los casos en los que la enfermedad misma se deriva de un tratamiento anterior. Mostramos a continuación algunas líneas de concordancia con este tipo de información:

L-Asparaginase is the major induction-phase agent for treatment of acute lymphoblastic leukemia (ALL) and an important adjuvant in treatment of non-Hodgkin's lymphoma (NHL). However, L-asparaginase- induced disturbances of clotting homeostasis may result in thrombosis or hemorrhage.

Successful treatment of acute lymphocytic leukemia (ALL) consists of the control of bone marrow and systemic disease as well as the treatment (or prevention) of sanctuary-site disease, particularly the central nervous system (CNS).

The treatment of infant acute lymphoblastic leukemia (ALL) continues to be a significant challenge for pediatric oncologists due to the high incidence of early relapses. Salvage regimens used to date have met limited success.

For a newly diagnosed patient with no prior treatment, untreated adult acute lymphocytic leukemia (ALL) is defined as an abnormal white blood cell count and differential, abnormal hematocrit/hemoglobin and platelet counts, abnormal bone marrow with more than 5% blasts, and signs and symptoms of the disease.

Although anthracyclines are part of the standard treatment of acute myelogenous leukemia (AML) and acute promyelocytic leukemia (APL), the role of Dzx in the treatment of AML or APL has not been established.

Mitoxantrone is an intravenous anthracenedione structurally related to the anthracycline antibiotics. This drug has been used for several years in the treatment of acute myelogenous leukemia (AML).

Recombinant interferon a is approved for use in the treatment of hairy cell leukemia and AIDS-related Kaposi's sarcoma.

Since myelosuppression is an anticipated consequence of both the leukemia and its treatment with chemotherapy, patients must be closely monitored during remission induction treatment.

The supportive care of patients with pancytopenia is a critical aspect of the treatment of acute leukemia, and this primarily involves the appropriate administration of blood products and management of infections.

High-dose chemotherapy, such as that employed in the treatment of leukemia and bone marrow transplantation (BMT) regimens, may produce severe mucositis.

Busulfan is an alkylating agent commonly used in the treatment of chronic myelogenous leukemia and in combination with cyclophosphamide in preparation for allogeneic bone marrow transplantation.

Since the discovery of the differentiating activity of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), the treatment of this disease has greatly improved.

Treatment of leukemia depends on the type of leukemia, certain features of the leukemia cells, the extent of the disease, and prior history of treatment, as well as the age and health of the patient.

Aggressive cases of T-LGL leukemia are usually treated with combination chemotherapy (CHOP-like regimen). The response rate is poor, and most patients die within one year of the start of treatment.

Preliminary data suggest that cumulative doses of greater than 2 grams per square meter of etoposide may confer higher risk. The risk of secondary leukemia after treatment with cisplatin, vinblastine, and bleomycin (PVB) may only be minimally elevated.

Por otra parte, con la sonda de conocimiento character* pudimos extraer información sobre diversas características de la enfermedad y sus tipos, como las mutaciones que contribuyen a la proliferación celular o el tipo de células implicadas en la enfermedad.

Such a separation of functional domains raises the possibility that mutations occurring at these regions may contribute to cell proliferation in the absence of differentiation, this being the most important characteristic in acute leukemia cells.

Cellular characteristics of acute leukemia cells simultaneously expressing CD13/CD33, CD7 and CD19. SO - Int J Hematol 1997;66(4):479-91 AD - Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan. AB

Likewise, hairy cell leukemia has a characteristic immunophenotype: CD5-, CD11c bright+, CD25+, CD103+, which distinguishes it from other CD5- B-cell lymphoproliferative disorders, including the morphologically similar splenic lymphoma with circulating villous lymphocytes.

These data (i) show that among characterized leukemia breakpoint regions 3q21 is unusually gene rich, (ii) provide new candidates for relevance to leukemia in 3q21, and (iii) suggest possibilities for chromatin configuration effects.

Large granular lymphocyte (LGL) leukemia is another type of chronic leukemia, characterized by larger lymphocytes containing conspicuous granules, which appear when examined under a microscope. These are not features of cells in other types of chronic lymphocytic leukemia.

B-chronic lymphocytic leukemia (CLL)is characterized by an accumulation of long-lived, resting B cells expressing the Bcl-2 protein. However, less than 10% of the CLL patients shows bcl-2 gene rearrangement in blood cells, using traditional Southern blotting analysis.

Large granular lymphocytic leukemia is characterized by lymphocytosis with a natural killer cell immunophenotype (CD2, CD16, and CD56) or a T-cell immunophenotype (CD2, CD3, and CD8).[6,7] These patients often have neutropenia and a history of rheumatoid arthritis.

The chromosome abnormalities that characterize chronic myelogenous leukemia can be detected by other techniques as well. A very sensitive test of blood or marrow cells, the polymerase chain reaction or PCR, can increase very small amounts of either RNA or DNA and make them more easily detectable.

With the recognition that many subtypes of leukemia are characterized by reproducible karyotypic abnormalities, a tremendous growth in the field of cytogenetics has been realized.

Adult T cell leukemia/lymphoma (ATLL) presents in an aggressive manner, with generalized lymph adenopathy, hepatosplenomegaly, cutaneous infiltration, hypercalcemia, lytic bone lesions, elevated LDH, and a profound leukemia characterized by pleomorphic CD4-positive T cells.

The characterization of antigens restricted to leukemia and hematopoietic tissues should make it eventually possible to produce specific and powerful antileukemic alloresponses in donor lymphocytes by adoptive immunotherapy or by vaccines. JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL Sensitivity of Helicobacter pylori

La sonda de conocimiento classif* nos ofreció información sobre las clasificación de tipos de leucemia, incluyendo algunas clasificaciones estándar usadas comúnmente por los científicos: Pure erythroid malignancies, such as Di Guglielmo disease (DG), in which the predominant immature elements are proerythroblasts, are excluded from the French-American-British (FAB) classification for acute leukemia and do not fit neatly into any of the categories of myelodysplasia.

ACUTE LEUKEMIAS: ALL AND AML PATHOLOGY AND CLASSIFICATION The diagnosis of acute leukemia requires the demonstration of leukemic cells in the bone marrow, peripheral blood, or extramedullary tissues. The bone marrow is typically hypercellular with a monomorphic infiltration of leukemic blasts and a marked reduction in normal bone marrow elements.

Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used.

Evaluate the prognostic significance of several disease/patient characteristics with regard to long-term outcome: age, initial WBC, presence of CNS leukemia, antecedent leukemia (preleukemia), cytogenetic abnormalities, FAB classification, various other cellular characteristics (e.g., surface antigens), status of the day 7 bone marrow, and alterations in cell cycle kinetics and cell cycle-regulated genes and oncogenes after 1 day of therapy.

Traditionally, patients with greater than 25% marrow blasts are classified as having B-cell leukemia and those with less than 25% marrow blasts are classified as having lymphoma.

These variables include clinical parameters at the time of diagnosis (e.g., age and white blood cell [WBC] count) and biologic features of the leukemic cells (e.g., immunophenotype, cytogenetics, and DNA content). The intensity of the therapeutic regimen is based on the prognostic classification of the child's leukemia.

These results indicate that objective classification of multifaceted phenotypes in leukemia can be achieved for analyzing multiparameter data in flow cytometry and further categorization into the prognostic subtypes.

The French-American-British (FAB) classification recognized LGL leukemia as one of four subgroups of chronic T-lymphoid leukemias.

In 1993, we proposed that LGL leukemias could be further classified into T-LGL leukemia and NK-LGL leukemia, depending on the cell lineage of the leukemic cells.

Most recently, the Revised European-American Lymphoma (REAL) classification has recommended that LGL leukemia be a distinct entity classified in the peripheral T-cell and NK-cell neoplasms.

Acute lymphocytic leukemia can be identified and classified on the basis of morphology and immunologic phenotype related to the stage of lymphoid differentiation.

According to the classification of chronic lymphocytic leukemia (CLL) proposed by A. I. Vorob'ev and M. D. Brilliant in 1983, benign CLL is a distinct form of CLL which is characterized by low level of absolute lymphocytosis, absent or mild peripheral lymphadenopathy, slow progression. No specific therapy is needed.

According to the French-American-British (FAB) proposal on the classification of chronic lymphoid leukemia (CLL), the disorder can be subdivided into typical and atypical CLL.

Chronic myelomonocytic leukemia (CMML) is usually classified as a form of MDS. The hallmark of CMML is an increase in the type of white cell called a monocyte.

Classification of leukemia is broadly related to the cell of origin (e.g., lymphoid or myeloid) as well as to the rapidity of the clinical course (e.g., acute or chronic), but modern categorizations have identified specific leukemias on the basis of biologic, antigenic, and molecular characteristics of these diseases.

In this regard, leukemia classified as lymphoid or myeloid by phenotype is also classified as a candidate for the corresponding chemotherapy protocol. Additionally, the subtype of leukemia based on the degree of differentiation and cell maturity influence prognosis, response to treatment, and median survival times

La sonda de conocimiento affect* nos permitió extraer líneas de concordancia en las que las que los autores tratan sobre los órganos y tipos celulares afectados por la enfermedad, o en las que se determinan los segmentos de población con mayor incidencia de la enfermedad:

Anticancer drugs given by IV injection or taken by mouth enter the bloodstream and affect leukemia cells in most parts of the body. However, the drugs often do not reach cells in the central nervous system because they are stopped by the blood-brain barrier.

Because those situations are unusual, researchers are now turning their attention to how variables like number of social contacts, vaccination, and breast feeding affect leukemia risk under less extreme conditions.

The other way is by the type of blood cell that is affected. Leukemia is either acute or chronic. In acute leukemia, the abnormal blood cells are blasts that remain very immature and cannot carry out their normal functions.

Hairy cell leukemia affects white blood cells called lymphocytes. Lymphocytes are made in the bone marrow and other organs.

Some patients develop sores in the eyes or on the skin. Leukemia also can affect the digestive tract, kidneys, lungs, or other parts of the body. In chronic leukemia, the abnormal blood cells may gradually collect in various parts of the body.

Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461. Journal of Clinical Oncology 15(2): 466-475, 1997.

This study measured plasma deoxycytidine in healthy adults and two leukemia patients and then determined how clinically relevant deoxycytidine levels would affect drug toxicity in human leukemia and lymphoma cells.

If leukemia affects a young person quickly, it is called "acute"; because it comes on suddenly and progresses rapidly without treatment. Almost all childhood leukemias are acute, but the disease is some times of the "chronic" type.

T-LGL leukemia affects elderly people. Approximately 60% of patients are symptomatic; recurrent infections secondary to chronic neutropenia, anemia, and rheumatoid arthritis are the main clinical features.

There are four types of myeloproliferative disorders: chronic myelogenous leukemia, polycythemia vera, agnogenic myeloid metaplasia, and essential thrombocythemia. Chronic myelogenous leukemia affects the cells that are developing into white blood cells, called granulocytes.

Leukemia also can affect the digestive tract, kidneys, lungs, or other parts of the body. In chronic leukemia, the abnormal blood cells may gradually collect in various parts of the body.

Leukemia inhibitory factor (LIF) affects the growth of carcinoma cells, and we thus analyzed its underlying mechanisms. Carcinoma cells constitutively express LIF mRNA, and 23 lines (92.0%) and all (100%) of 25 lines express LIF receptor mRNAs of LIFRbeta and gp130, respectively.

In MDS, the production of any or all types of blood cells are affected, as opposed to leukemia, in which only one type of blood cell is overproduced. Because red cells, white cells and platelets are of poor quality, many are destroyed before they leave the bone marrow.

La sonda de conocimiento risk nos fue muy útil para obtener información sobre los principales factores de riesgo para el desarrollo la enfermedad, entre los que cabe destacar el elevado número de contextos en los que se hacía referencia a la leucemia derivada del tratamiento de otro cáncer¹⁴⁸ y otros aspectos importantes, como los riesgos de afecciones derivadas de la leucemia.

The risk of an acute leukemia 2-3 years after therapy for SCLC ranged between 2-18% (Johnson DH 1986, Zulian 1993). Both radiation therapy and cytotoxic drugs have been implicated in second cancers (Tucker 1997).

Long-term survivors are at increased risk of developing acute leukemia, the myelodysplastic syndrome, or paroxysmal nocturnal hemoglobinuria. LABORATORY DIAGNOSIS The diagnosis of aplastic anemia and the assessment of its relative severity depend on a thorough laboratory evaluation. The peripheral blood usually shows pancytopenia.

Although clinical features are important prognostic indicators, genetic alterations of leukemic blasts may be better predictors of outcome for acute leukemia patients. We therefore favor risk-adapted therapy based on classification schemes that incorporate both genetic and clinical features.

The risk of acute leukemia at 10 years following therapy with doxorubicin + bleomycin + vinblastine + dacarbazine (ABVD) appears to be less than 1%.[8] An increase in second solid tumors has also been observed, especially cancers of the colon, lung, bone, thyroid, and breast.

The risk of acute leukemia has been correlated to the duration of melphalan treatment. As with other secondary acute myeloid leukemias, treatment is difficult and prognosis is very poor.

The type of treatment administered may influence the later risk of secondary acute leukemia, as combined modality therapy with certain chemotherapeutic regimens and irradiation is associated with increased risk compared with either treatment alone.

Secondary leukemias: Several reports of elevated risk of secondary acute leukemia, primarily non-lymphocytic, have appeared.[20] In some cases, they were associated with the prolonged use of alkylating agents or with the use of radiation.[21] Etoposide-containing regimens are also associated with a risk of secondary acute leukemias, usually in the myeloid lineage,

The risk of a secondary acute leukemia with irradiation alone is much less than with chemotherapy. There may also be a dose response-effect: with an increased dose of chemotherapy there is an increased risk of secondary leukemia; this risk may be increased after splenectomy.

Neutrophils and monocytes/ macrophages are the essential host defense factors against the zygomycetes.[4] Patients with acute leukemia are at high risk of developing mucormycosis as a result of prolonged neutropenia.

People with human T-cell lymphotropic virus type I (HTLV-1)-associated leukemia/lymphoma have a high risk of developing hypercalcemia.

Usando éstas y otras sondas de conocimiento (entre las que se incluyen prognosis, surviv*, therap*, remission, associat*, result* y relat*) pudimos obtener un listado de relaciones y valores de dichas relaciones muy completo. La siguiente tarea que debemos acometer es la representación formalizada de dicha información en la ontología de Mikrokosmos (§ 5.3.3). Para ello, hemos convertido en conceptos las relaciones y sus valores que no estaban incluidos en la ontología, colocándolos sus lugar correspondiente de la jerarquía y hemos usado las relaciones identificadas para enriquecer la estructuración conceptual de la ontología, relacionando unos conceptos con otros en la ontología. En el apéndice II mostramos la forma en la que parte de la información sobre la estructura del subdominio de la leucemia ha sido representada, usando los mecanismos de representación y el sistema gestor de ontologías detallado en el apartado 5.4. En el apartado que sigue mostraremos brevemente la forma en la que hemos representado en la ontología la información obtenida usando el tipo de búsquedas mostradas en este apartado.

Notas

¹⁴⁸ En referencia a los efectos secundarios derivados del tratamiento del cáncer, es interesante observar la aparición del compuesto "risk-adapted therapy", como se muestra en la tercera concordancia de este grupo.