RESUMEN
Dysmetabolic iron overload syndrome is a rare event causing hepatic impairment with serious long-term side effects. Here, we describe a case of metabolic syndrome-related hepatic iron overload that showed a rapid, effective, and safe response to erythrocytapheresis. J. Clin. Apheresis 31:443-447, 2016. © 2015 Wiley Periodicals, Inc.
Asunto(s)
Citaféresis , Transfusión de Eritrocitos/normas , Sobrecarga de Hierro/terapia , Hepatopatías/metabolismo , Humanos , Sobrecarga de Hierro/complicaciones , Hepatopatías/etiología , Síndrome Metabólico , Seguridad del PacienteRESUMEN
BACKGROUND/AIM: Philadelphia-positive acute lymphoblastic leukemia (Ph+ B-ALL) is caused by the malignant transformation of lymphoid cells induced by BCR-ABL1 constitutive catalytic activity. BCR-ABL1 tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML) cells, inducing durable hematological, cytogenetic and molecular responses. However, in Ph+ B-ALL - as in CML progressing to blast crisis - TKIs fail to maintain disease remission. We, therefore, wanted to investigate if dual targeting of BCL-2 and BCR-ABL1 would be more effective in killing Ph+ B-ALL cells. MATERIALS AND METHODS: p210-B-ALL CD34-positive cells were used to evaluate the BCR-ABL expression and pharmacological targeting of BCL-2, by venetoclax, alone or in combination with BCR-ABL1 inhibition. RESULTS: We demonstrated the cytotoxic effect of BCL-2 inhibition and that dual targeting of BCL-2 and BCR-ABL1 with venetoclax and nilotinib further increases this cytotoxicity. CONCLUSION: BCL-2 is a key survival factor for primary Ph+ B-ALL cells and its inhibition - alone or in combination with a BCR-ABL1 TKI - should be further investigated as a potential therapeutic strategy for these patients.
Asunto(s)
Proteínas de Fusión bcr-abl/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Humanos , Terapia Molecular Dirigida , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Pronóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Acute myeloid leukemia is well characterized by chromosomal aberrations that correspond to various subtypes of acute leukemias. The t(8;21)(q22;q22) is a frequent chromosomal abnormality strongly associated with acute myeloblastic leukemia with maturation (AML-M2), but is rarely associated with other subtypes. Translocation involving a third chromosome could produce new genetic rearrangements that lead to leukemogenesis. PATIENTS AND METHODS: Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) were performed to identify the karyotype. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the AML1/ETO transcript. RESULTS/CONCLUSION: We herein report a novel rearrangement with a three-way translocation involving chromosomes 8, 21 and another unknown chromosome, in an 83-year-old female patient diagnosed as AML-M4, with an ALM1/ETO negative transcript. This is an uncommon case of AML-M4 with three-way translocation in a new variant of t(8;21) acute myeloid leukaemia. The detailed mechanism of different phenotype expression is unclear. Further study is needed to identify the leukemogenetic transformation resulting from t(8;21) translocation.