RESUMO
The basis for persistence of leukemic stem cells in the bone marrow microenvironment remains poorly understood. We present evidence that signaling cross-talk between α4 integrin and Abelson interactor-1 (Abi-1) is involved in the acquisition of an anchorage-dependent phenotype and drug resistance in Bcr-Abl-positive leukemia cells. Comparison of Abi-1 (ABI-1) and α4 integrin (ITGA4) gene expression in relapsing Bcr-Abl-positive CD34+progenitor cells demonstrated a reduction in Abi-1 and an increase in α4 integrin mRNA in the absence of Bcr-Abl mutations. This inverse correlation between Abi-1 and α4 integrin expression, as well as linkage to elevated phospho-Akt and phospho-Erk signaling, was confirmed in imatinib mesylate -resistant leukemic cells. These results indicate that the α4-Abi-1 signaling pathway may mediate acquisition of the drug-resistant phenotype of leukemic cells.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas do Citoesqueleto/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Microambiente Tumoral/efeitos dos fármacos , Animais , Antígenos CD34/metabolismo , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Integrina alfa4/metabolismo , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Complexo de Endopeptidases do Proteassoma/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
The authors present the case of a 35-years-old female with severe bronchial asthma non-responding to treatment, mobile infiltrative pulmonary images on chest X-ray considered and treated first as pulmonary tuberculosis smear-negative, maculo-papular skin lesions on the limbs and a high percentage of eosinophils in peripheral blood. The diagnosis was settled by histologic examination of the skin lesions. The evolution was very good with high doses of oral corticosteroids.