RESUMO
Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PAD chemotherapy (bortezomib, doxorubicin and dexamethasone). Comparative proteomic analysis was conducted on pretreatment plasma cells from 77 proteasome inhibitor naïve patients treated subsequently with PAD due to RRMM. To increase data confidence we used two independent proteomic platforms: isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and label free (LF). Proteins were considered as differentially expressed when their accumulation between groups differed by at least 50% in iTRAQ and LF. The proteomic signature revealed 118 proteins (35 up-regulated and 83 down-regulated in ≥ VGPR group). Proteins were classified into four classes: (1) involved in proteasome function; (2) involved in the response to oxidative stress; (3) related to defense response; and (4) regulating the apoptotic process. We confirmed the differential expression of proteasome activator complex subunit 1 (PSME1) by enzyme-linked immunosorbent assay. Increased expression of proteasomes and proteins involved in protection from oxidative stress (eg., TXN, TXNDC5) plays a major role in bortezomib resistance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Recidiva Local de Neoplasia/metabolismo , Idoso , Antineoplásicos , Apoptose , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Proteômica , Espectrometria de Massas em Tandem , Tiorredoxinas/química , Resultado do TratamentoRESUMO
B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common form of leukemia affecting adults in Europe and North America. Large B-cell lymphoma known as Richter's syndrome (RS) may develop approximately in 3-15 % patients. Furthermore, other hematological malignancies may also occur as RS variants, among them-Hodgkin lymphoma (HL). CLL/SLL transformation into HL is observed in about 0.5 % of patients, and till now, fewer than 100 cases have been reported in the medical literature. We present two cases of HL transformation of CLL/SLL and review the previously published literature.