Blood: Characteristics of the evolution and diffusion of multiple myeloma clones

Cloning evolution drives the progression, spread and recurrence of tumors of multiple myeloma (MM), and most patients die from relapsed diseases.
this multi-stage process requires tumor cells to enter the bloodstream, seep out, and be implanted into distant bone marrow (BM).
in a recent study published in Blood, researchers developed a fluorescent or DNA barcode cloning tracking system on models of MM PrEDiCT heterogeneity transplanted mice to study cloning behavior in BM micro-environments.
diffusion model of fluorescent MM cells showed that only a few clones that successfully adapted to the BM micro-environment could enter the bloodstream and be planted in long-range BMs.
RNA sequencing of primary and distant MM cells showed that progress signals were activated in turn as human MMs progressed, and were significantly associated with total survival when evaluated against patient data sets.
expressions of HMGA1 and PA2G4 in different samples were calculated to predict that 28 genes might be the main regulatory gene (MRS) for MM progress.
HMGA1 and PA2G4 were validated in the PrEDiCT model through CRISPR/Cas9, and HMGA1 and PA2G4 were also found to be significantly missing at distant bone marrow sites, suggesting that they played a role in the progress and diffusion of MM.
, the absence of HMGA1 and PA2G4 also affects the proliferation, migration and adhesion of MM cells.
overall, the study model successfully summarizes the key characteristics of the progression of human MM disease and identifies potential new therapeutic targets for MM.