Practice question

Primary plasma cells cannot be cultured long term because they activate intrinsic mitochondrial apoptosis via Bim upregulation when removed from survival niche provided by stromal cell contact, interleukin-6, and BAFF, plus replicative senescence triggered by telomere shortening each division. Myeloma cells circumvent these barriers through multiple oncogenic lesions: expression of hTERT telomerase reverse transcriptase adding TTAGGG repeats preventing crisis, disruption of p53-MDM2 axis, loss of cyclin dependent kinase inhibitors p16 and p21, autocrine loops via IGF-1 and interleukin-6 constitutively activating JAK-STAT3, and anti-apoptotic proteins Bcl-2, Mcl-1, Bcl-xL sequestering Bax-Bak. Metabolically they exhibit enhanced aerobic glycolysis and glutaminolysis supporting high rate immunoglobulin synthesis of 20 to 50 picograms per cell per day needed for commercial manufacture. Specificity remains encoded entirely by B cell derived VDJ sequences while unlimited division derives solely from tumor genome. Without immortality contribution, antibody secreting clones exhaust after few doublings, master cell banking for regulatory filing impossible, and large-scale therapeutic production economically unfeasible, underscoring myeloma purpose for perpetuating culture.