RESUMEN
The AML1 gene, located in the chromosomal band 21q22, belongs to the runt domain family of genes and encodes the subunit of the core-binding factor (CBF). AML1 is normally expressed in all hematopoietic lineages and is essential for the transcriptional regulation of a number of hematopoietic specific genes. In acute leukemia three types of abnormality of AML1 have been observed -- chromosomal translocations, point mutation and duplication or amplification of the unrearranged gene. The most common origin of extra copies of the AML1 gene is polysomy of chromosome 21 or a partial duplication of the long arm of chromosome 21, less frequently ring, isochromosome or the tandem repetition of chromosome 21. In the study 13 children and 5 adults with ALL and AML or MDS, respectively, have been included. Using standard G-banding and dual color FISH analyses, gain of AML1 originated in polysomy of chromosome 21 in each group of patients was proved. True high-level amplification was not observed but some uncommon changes in noteworthy association with other chromosome aberrations, age or diagnoses were presented.
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Amplificación de Genes , Leucemia/genética , Enfermedad Aguda , Adulto , Anciano , Niño , Preescolar , Aberraciones Cromosómicas , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana EdadRESUMEN
Chronic myeloic leukemia (CML) is a malignant disease of hematopoietic stem cell characterized by the bcr/abl gene rearrangement. Allogeneic transplantation of stem cells (SCT) is a routinely used treatment method of patients with this diagnosis and remains the only curative mode of treatment. From January 1990 to December 2002, 78 patients with CML underwent allogeneic transplantation and were examined at the Department of Genetics in the National Cancer Institute in Bratislava. Using conventional cytogenetic and FISH 6 patients (7.7%) showed additional chromosomal changes before SCT. These patients had statistically worse post transplantation prognosis compared to the patients without additional changes before SCT (mean survival in month+/-standard error (58.08 (+/-6.70) vs. 5.17 (+/-0.98), p-value=0.001), patient mortality (67% vs. 31%)). In addition five other variables were evaluated for transplant outcome, namely, patient's age at the time of transplantation, sibling or non-sibling donor, higher than 1st chronic phase CML, time from diagnosis to transplantation and sex of donor and recipient. Only the comparison of HLA-identical sibling transplantation to unrelated donor transplantation was statistically significant (mean survival in month- 56.6 (+/-7.2) vs. 13 (+/-0.0), patient mortality 31% vs. 67%).
Asunto(s)
Aberraciones Cromosómicas , Rechazo de Injerto/genética , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Adulto , Niño , Femenino , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Imatinib mesylate (STI 571; Glivec) is a potent and selective tyrosine kinase inhibitor. The introduction of imatinib has chanced the philosophy of mechanisms of cancer therapy and already changed current management of patients with chronic myeloid leukemia (CML). A total of 49 patients with later chronic phase CML in whom previous therapy with interferon alpha had failed were treated with 400 mg of oral imatinib daily. Patients were evaluated for hematologic and cytogenetic responses. Time to progression, survival, and toxic effects were also evaluated. Complete hematologic responses were reported for 48 of 49 patients studied (98 percent). The median time to a complete hematologic response was 1.2 month; 89% of patients who had a response did so within 4 months. Imatinib induced major cytogenetic responses in 73%; 62% had a complete responses. After a median follow-up of 18 months, CML had not progressed to the accelerated or blast phases in an estimated 98% of patients, and 100 percent of the patients were alive. Grade 3 or 4 nonhematologic toxic effects were manageable. No one of patients discontinued treatment due to of drug-related adverse events, and no treatment-related deaths occurred. The results of current study indicate that imatinib has a significant therapy benefit in CML patients in whom treatment with IFN alpha had failed. Therefore, has favorably changed the prognosis for patients with chronic myelogenous leukemia.
Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Administración Oral , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Benzamidas , Resistencia a Antineoplásicos , Femenino , Humanos , Mesilato de Imatinib , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Pronóstico , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Resultado del TratamientoRESUMEN
In a group of 102 children with different immunological subtypes of acute leukemia, both lymphoblastic and nonlymphoblastic, the clinical parameters - event free survival and overall survival were correlated with numerical and structural chromosomal abnormalities. In a group of 80 ALL patients genetic abnormalities were observed in 40 patients, from those 19 of numerical type, 17 of structural type and 4 with both, numerical and structural anomalies. From the whole ALL group observed 23 patients (28.75%) died. In 10 died patients genetic abnormalities were found and in 6 cases less mature T-phenotype ALL has been documented. It seems, therefore, that immature T-phenotype with pathological karyotypes of all types of genetic anomalies presents the most risk group of patients of which all children died. ALL patients, as a whole, with pathological karyotype have shown significantly lower event free survival rate, comparing to the group of ALL patients with normal karyotype. Overall survival rate was also lower in the first group, but statistically not significant. In T-ALL patients, in both groups, with and without pathological karyotype, event free survival rate and overall survival rate were also lower in the first group, but statistically not significant. In B-ALL patients with pathological karyotypes vs. normal ones overall survival rate was lower in the first group, but statistically not significant. There was no difference in overall survival rate in these patients between pathological and normal karyotypes. In ANNL group of patients pathological karyotype was observed in 14 of them, with numerical anomalies in 6 patients, structural in 4 patients and both of them - numerical + structural in 4 children. From the whole ANLL group observed 11 (50%) patients died during the follow-up period (9 in relapse and 2 of treatment complications). From 11 died patients in 81.8% pathological karyotype was present. The prevalence of pathological karyotypes was observed in less mature M0-M2 ANLL subtype (71.4%). ANLL patients with pathological karyotype have shown significantly lower event free survival rate (in one of the two statistical log-rank analyses), comparing to the group of ANLL patients with normal karyotype. Overall survival rate was also lower in the first group, but statistically not significant. The presence/absence of CD34 marker expression in blast cells of our group of acute leukemia patients did not show any difference in event free survival and overall survival rates.