Plasma Cell Myeloma (PCM)

Overview

Plasma cell myeloma (PCM), commonly known as multiple myeloma, is a hematologic malignancy of terminally differentiated B cells (plasma cells) that accumulate in the bone marrow. It is characterized by overproduction of monoclonal immunoglobulin, bone marrow infiltration, bone destruction, and renal insufficiency. PCM is the second most common hematologic malignancy and remains incurable in most patients despite advances in therapy.

Cohorts in the corpus

  • cellline_ccle_broad: Multiple myeloma cell lines included among 947 lines in the CCLE pharmacogenomic panel.

Recurrent alterations

  • CCLE profiling included PCM cell lines; high IGF1 and IGF1R expression in 12 of 14 multiple myeloma cell lines correlated with enhanced sensitivity to the IGF-1 receptor inhibitor AEW541 PMID:22460905.
  • WES/WGS of 203 plasma cell myeloma patients identified 11 significantly mutated genes (KRAS, NRAS, BRAF, TENT5C, TP53, DIS3, TRAF3, CYLD, RB1, PRDM1, IRF4) and showed pervasive clonal heterogeneity (most patients had ≥3 subclones); BRAF inhibitors paradoxically promoted growth in BRAF-WT KRAS/NRAS-mutant MM cell lines PMID:24434212.

Subtypes

  • Molecularly classified by translocation status (t(4;14), t(11;14), t(14;16)) and copy-number profiles (del(17p), amp(1q)); IGF-1R dependency may be broadly distributed across subtypes based on CCLE data.

Therapeutic landscape

  • IGF-1 receptor inhibitor AEW541 showed enhanced sensitivity in 12/14 PCM cell lines in the CCLE screen, with high IGF1 and IGF1R expression as correlates; IGF-1R inhibitors represent a candidate clinical direction for multiple myeloma PMID:22460905.
  • Hematologic lineages including PCM showed preferential sensitivity to panobinostat (HDAC inhibitor) in CCLE pharmacogenomic profiling PMID:22460905.

Sources

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