Gene Expression Profiling (GEP) of Whole Bone Marrow Biopsies (BMB) in Multiple Myeloma (MM) – Relationship to Plasma-Cell (PC)-Based GEP-Defined Risk and Molecular Subgroups

Abstract 3953

PC-GEP provides great insight into MM heterogeneity as defined by 7 distinct molecular subgroups, along with clinical correlates and prognosis, as identified by the GEP-70 model. As is now increasingly appreciated in MM, a close interaction exists between PC and the bone marrow micro-environment (ME), which results not only in MM bone disease but also contributes to MM progression and drug resistance. We postulated that such interaction could be revealed by performing GEP both on PC and the bone marrow biopsy (BMB) proper. In addition to having demonstrated that BMB-GEP can attain a normal (NL)-like status in comparison with NL donors with favorable prognostic implications, we are now reporting on paired comparisons of BMB-GEP and PC-GEP toward elucidating whether different molecular subgroups (MOLS) (namely, CD-1, CD-2, MAF, MAF-B, MS, HY, PR) and GEP-70-defined prognostic risk groups (RISK) engage the ME differentially. Toward this end, a recently defined BMB-GEP model of 65 genes, distinguishing NL, MGUS/AMM, MM and MM-CR, was applied to determine whether linkage existed to MOLS and RISK. Indeed, based on mean-based statistics, BMB-65 scores varied among MOLS and RISK (both p=0.013). A negative correlation (R=-0.204) existed between BMB-65 and PC-70 scores (p=0.0014). Further analysis within MOLS revealed significant negative correlations within MF (R=-0.57, p=0.0087) and MS subtypes (R=-0.33, p=0.037). None of the other MOLS showed any significant correlations. This is the first demonstration in patient MM samples that MOLS may engage the ME differentially. The more pronounced inverse correlations of MF and MS subtypes reveal a counter-relationship between RISK and BMB-65 score. This implies that with greater aggressiveness of PC, the BMB appears less NL-like, and is thus more modified to support the malignant PC processes. More detailed analyses will be presented in the context of other GEP and clinical parameters, specifically concerning the prognostic implications of BMB scores at baseline.

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