RESUMO
OBJECTIVE: To explore the morphologic, immunophenotypic, cytogenetic and clinical features of acute lymphoblastic leukemia (ALL) patients with dicentric (9; 20) (p11 - 13; q11). METHODS: Chromosome specimens of bone marrow cells were prepared by direct method and/or short-time culture. Karyo-typing was performed by R-banding technique. Dual-color fluorescence in situ hybridization (FISH) was performed using both chromosome 9 classical satellite probe and chromosome 20 alpha-satellite probe in one patient. RESULTS: The two ALL patients were positive for CD10 and HLA-DR, showing of B cell origin. Both patients had dicentric (9; 20): case 1 was 45, XY, der (9) t (9; 20) (p11; q11), -20[20]; case 2 was 45, XX, der (9) t (9; 20) (p13; q11), t (9; 22) (q34; q11), -20[10]/46, idem, +8[16]/47, idem, +8, +21[14]. Mutual translocation between chromosomes 9 and 20 of the dicentric chromosome was confirmed by FISH in one patient. CONCLUSIONS: Dicentric (9; 20) (p11 - 13; q11) is a rare recurring chromosome abnormality associated with ALL. Because of the subtle nature of the translocation, FISH is essential for the detection of this abnormality.
Assuntos
Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 9/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Adulto , Sequência de Bases , Bandeamento Cromossômico , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Análise de Sequência de DNARESUMO
OBJECTIVE: To investigate the mechanism of multi-drug resistance of K562-n/VCR cell line with both bcr-abl and mdr-1 expressions by clustering analysis of differential gene expression profiles. METHODS: By DNA microarray technique, genes differentially expressed by K562-n/VCR and K562-n cell lines were identified and analyzed. RESULTS: DNA microarray analysis of K562-n/VCR and K562-n cells was repeated three times and revealed 58 genes significantly differentially expressed among 12,800 genes arrayed. All but one was up-regulated in K562-n/VCR cells. The only gene down-regulated was a-myb. The up-regulated genes were MDR-associated genes, oncogenes, cytoskeleton, protein kinases and phosphatases, apoptotic and antiapoptotic factors, metabolism, transcriptional regulators associated with stress response, cell cycle checkpoint control, and genes for signal transduction proteins. CONCLUSION: These results indicate that, besides MDR-associated genes, other known and unknown genes may also be involved in the mechanism of multi-drug resistance.
Assuntos
Resistência a Múltiplos Medicamentos/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Animais , Humanos , Células K562 , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Vincristina/farmacologiaRESUMO
OBJECTIVE: To study the synergistic effect of STI571, an inhibitor of tyrosine kinase in combination with arsenic trioxide (As(2)O(3)) on a multidrug-resistant leukemia cell line expressing bcr-abl. METHODS: The cytotoxic effect of STI571 alone or in combination with different concentrations of As(2)O(3) on both bcr-abl and mdr1 positive leukemia cell line K562-n/VCR was detected by MTT method. RESULTS: The cytotoxic effect of STI571 (1 micromol/L) combined with As(2)O(3) at concentrations 10(-5), 10(-6), 10(-7), 10(-8) mol/L (IC(50) 0.155 micromol/L) on K562-n/VCR cells was significantly higher than that of As(2)O(3) alone (IC(50) 1.879 micromol/L). The synergistic interaction on K562-n/VCR cells increased the cytotoxic effect by 12.1-fold. CONCLUSION: Combination of STI571 with As(2)O(3) has a synergistic inhibiting effect on leukemia cells expressing bcr-abl and mdr1.
Assuntos
Arsenicais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Óxidos/farmacologia , Piperazinas/farmacologia , Pirimidinas/farmacologia , Antineoplásicos/farmacologia , Trióxido de Arsênio , Benzamidas , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Genes MDR , Genes abl , Humanos , Mesilato de Imatinib , Concentração Inibidora 50 , Células K562 , Proteínas Tirosina Quinases/antagonistas & inibidores , Vincristina/farmacologiaRESUMO
OBJECTIVE: Diagnosis of a case with congenital dyserythropoietic anemia (CDA). METHODS: Routine tests for hemolysis were carried out. The activities of erythrocyte enzymes were measured according to the methods recommended by international committee for standardization in hematology (ICSH). The quantity and quality of erythrocyte membrane proteins were analyzed with 4% - 15% sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis (SDS-PAGE). The membrane ultrastructure of erythrocyte from bone marrow was observed under transmission electron microscope (TEM). RESULTS: The main results were: (1) Bone marrow morphology revealed erythroid hyperplasia and 0.10 symmetrically binucleated late erythroblasts. The erythrocytes in peripheral blood showed anisocytosis and hypochromia. (2) The intracellular iron was 0.98 and the storage iron was strongly positive in bone marrow. The serum ferritin was 1607 micro g/L. The content of blood sugar was 27.5 mmol/L. (3) Ham test was negative in his own acidified serum but positive in the group-compatible sera. (4) A quick mobile H band was seen in hemoglobin electrophoresis. H inclusion test was positive. (5) SDS-PAGE demonstrated that the migration of band 3 protein of erythrocyte membrane in an electric field was faster (110%) than that of normal controls and the relative contents of band 1, band 3, band 4.1 were reduced to various extent. (6) "Double membrane" with gap and shedding was observes under TEM. CONCLUSIONS: The final diagnosis of the case was CDAII, also called HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum), accompanied with alpha thalassemia and secondary siderosis and diabetes.
Assuntos
Anemia Diseritropoética Congênita/patologia , Membrana Eritrocítica/ultraestrutura , Proteínas de Membrana/sangue , Adulto , Anemia Diseritropoética Congênita/sangue , Anemia Diseritropoética Congênita/complicações , Medula Óssea/patologia , Diabetes Mellitus/etiologia , Eletroforese em Gel de Poliacrilamida , Membrana Eritrocítica/metabolismo , Humanos , Masculino , Siderose/etiologia , Talassemia alfa/complicaçõesRESUMO
To explore the possibility of leukemia cell line of both bcr-abl and mdr-1 positive were cross-resistant to tyrosine kinase inhibitor STI571 and its reversal way, the inhibitory effect of STI571 on K562-n/VCR cells was detected with MTT method and reverse effects of CsA, TAM, IFN-alpha and CsA cominated with IFN-alpha were observed. The results showed that K562-n/VCR cell line expressing bcr-abl and mdr1 positive was resistant to STI571, and could be reversed by 5.18, 1.82 and 1.67-fold respectively, when treated with CsA, TAM, and IFN-alpha. It could be reversed by 34.87-fold with combination of half-dose CsA and IFN-alpha. In conclusion, amplification of mdr1 gene may contribute to drug-resistance of bcr-abl positive leukemic cells against STI571. The reversal agents, CsA, TAM and IFN-alpha show obviously reverse effects on drug-resistance. The combination of half-dose of both CsA and IFN-alpha display stronger effect than the full dose of either.
Assuntos
Antineoplásicos/farmacologia , Leucemia/tratamento farmacológico , Piperazinas/farmacologia , Pirimidinas/farmacologia , Benzamidas , Ciclosporina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Genes MDR , Genes abl , Humanos , Mesilato de Imatinib , Interferon-alfa/farmacologia , Células K562 , Leucemia/genética , Tamoxifeno/farmacologiaRESUMO
To analyze the relation of early immune reconstitution with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (all-HSCT), the changes of CD3(+), CD4(+), CD8(+), CD25(+) and CD69(+) cells in peripheral blood from 26 patients with hematologic malignancies were assayed by flow cytometry within 2 months after allo-HSCT. All patients achieved hematopoietic reconstitution, and grade I and II - IV GVHD were developed in 9 and 5 patients, respectively. CD25(+) cells were increased in patients aGVHD at week 2 after transplantation and the peak value was appeared at week 3. The increase of CD25(+) cells was preceded the occurence of clinical signs of aGVHD. The maximal levels of CD25(+) cells increase correlated significantly with the severity of aGVHD. The increase of CD25(+) cells was declined along with remission of aGVHD signs. Our results suggest that analyzing immune reconstitution after allo-HSCT could predict occurence of aGVHD, and CD25(+) cell increase prior occurence of aGVHD is predictive marker for aGVHD.