Transcriptional Characterization of a Prospective Series of Primary Plasma Cell Leukemia Revealed Signatures Associated with Tumor Progression and Poorer Outcome

Abstract

Purpose: Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia that presents either as a progression of previously diagnosed multiple myeloma, namely secondary PCL, or as initial manifestation of disease, namely primary PCL (pPCL). Although the presenting signs and symptoms include those seen in multiple myeloma, pPCL is characterized by several aspects that define a more aggressive course. Here, we have investigated the transcriptome of pPCLs and correlated differential expression profiles with outcome to provide insights into the biology of the disease. Experimental Design: The expression profiles of 21 newly diagnosed pPCLs included in a multicenter prospective clinical trial were generated using high-density microarray, then evaluated in comparison with a representative series of patients with multiple myeloma and in association with clinical outcome. Results: All but one of the pPCLs had one of the main immunoglobulin heavy-chain locus translocations, whose associated transcriptional signatures resembled those observed in multiple myeloma. A 503-gene signature distinguished pPCL from multiple myeloma, from which emerged 26 genes whose expression trend was associated with progressive stages of plasma cells dyscrasia in a large dataset from multiple institutions, including samples from normal donors throughout PCL. Finally, 3 genes were identified as having expression levels that correlated with response to the first-line treatment with lenalidomide/dexamethasone, whereas a 27-gene signature was associated with overall survival independently of molecular alterations, hematologic parameters, and renal function. Conclusions: Overall, our data contribute to a fine dissection of pPCL and may provide novel insights into the molecular definition of patients with poorer prognosis. Clin Cancer Res; 19(12); 3247–58. ©2013 AACR.

DEPTOR maintains plasma cell differentiation and favorably affects prognosis in multiple myeloma

“…We confirmed these results using two different microarray studies (GSE16558, and GSE39925 at GEO repository) [27, 29]. Next, we decided to quantify DEPTOR protein levels by capillary electrophoresis immunoassay in myeloma cells from 24 MM patients treated according to the Spanish GEM2010 trial.…”

Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma

“…Because we could not add to the results of FISH due to the lack of data, we would need to attempt a reanalysis of OS including the FISH results. Recent studies have shown new prognostic factors, including miRNA and gene expression profiles in pPCL, which correlated with treatment response and survival [29,30,31]. In the future, we need to incorporate these data in the prognostic analysis of pPCL.…”

Inactivation of CK1α in multiple myeloma empowers drug cytotoxicity by affecting AKT and β-catenin survival signaling pathways

“…Details regarding the source of all HMCLs have been previously reported [31, 45, 46] and recently authenticated by STR profiling and/or gene mutational analyses. For gene expression analysis, samples were profiled on the GeneChip Human Gene 1.0 ST array (Affymetrix, CA, USA) as described [47]. The raw intensity expression values were processed by Robust Multi-array Average procedure (RMA) [48] with the re-annotated Chip Definition Files from BrainArray libraries version 19.0.0, available at http://brainarray.mbni.med.umich.edu.…”