RESUMO
IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all MM. It should be distinguished from malignant neoplasms of B cells with plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma with plasmacytic differentiation. Plasma cell leukemia (PCL) is a rare and aggressive variant of MM characterized by the presence of circulating plasma cells. We present a case report of a patient who presented with IgM MM in primary PCL phase with high-risk cytogenetics. To our knowledge, this is the first reported case of IgM MM with primarily leukemic presentation in the era of novel drugs. We demonstrate that it is important to distinguish IgM MM from WM and review the data from clinical trials that was used to devise a treatment strategy for this high-risk patient. This case adds to the understanding of the diagnosis and management of IgM MM in leukemic phase.
Assuntos
Leucemia Plasmocitária/etiologia , Mieloma Múltiplo/diagnóstico , Idoso , Deleção Cromossômica , Cromossomos Humanos Par 17 , Terapia Combinada , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulina M/análise , Imunoglobulinas/análise , Leucemia Plasmocitária/diagnóstico , Leucemia Plasmocitária/prevenção & controle , Mieloma Múltiplo/genética , Mieloma Múltiplo/fisiopatologia , Mieloma Múltiplo/terapia , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnósticoRESUMO
Aberrant DNA methylation plays a relevant role in multiple myeloma (MM) pathogenesis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that recently emerged as master regulator of gene expression by targeting protein-coding mRNAs. However, miRNAs involvement in the regulation of the epigenetic machinery and their potential use as therapeutics in MM remain to be investigated. Here, we provide evidence that the expression of de novo DNA methyltransferases (DNMTs) is deregulated in MM cells. Moreover, we show that miR-29b targets DNMT3A and DNMT3B mRNAs and reduces global DNA methylation in MM cells. In vitro transfection of MM cells with synthetic miR-29b mimics significantly impairs cell cycle progression and also potentiates the growth-inhibitory effects induced by the demethylating agent 5-azacitidine. Most importantly, in vivo intratumor or systemic delivery of synthetic miR-29b mimics, in two clinically relevant murine models of human MM, including the SCID-synth-hu system, induces significant anti-tumor effects. All together, our findings demonstrate that aberrant DNMTs expression is efficiently modulated by tumor suppressive synthetic miR-29b mimics, indicating that methyloma modulation is a novel matter of investigation in miRNA-based therapy of MM.
