Blood:JAK-STAT pathrapy regulates myeloma CD38 expression and can be used as a therapeutic target.

Anti-CD38 monoclonal antibody (MoAb) therapy, including daratumumab (Daremu monoantigen), is effective for newly diagnosed, relapsed multiple myeloma (MM).
In this study, Ogiya and others detected soluble factors that regulate CD38 expression and found that they were associated with sensitivity to DARA-mediated antibody-dependent cytotoxicity (ADCC) in the bone marrow (BM) micro-environment.
important, the original BM substation stem cell (BMSC) media on the liquid (BMSC-sup) and white melebin 6 (IL-6) can reduce CD38 expression and weaken THEA-mediated ADCC.
BMSC-sup's cytokine spectrum and MM cell line full gene range gene-editing knockout screening tests found and confirmed that THEK-STAT3 signaling path is mediated by CD38, while JAK-STAT1 path is mediated by CD38.
low STAT3 can abolish BMSC-up and IL-6 induced MM cell line CD38 reduction.
, the researchers also confirmed that STAT3 and CD38 were negatively related in primary MM cells.
to assess the potential clinical relevance, the researchers further studied the pharmacological inhibition of the JAK-STAT path path to BMSC-sup-induced CD38 reduction.
JAK inhibitor Russotinib inhibits STAT3 phosphorylation of MM cells, which in turn increases the CD38 expression of MM cell line and patient MM cells, ultimately enhancing THEA-mediated ADCC for MM cell line.
in summary, this study shows that CD38 expression on MM cells in BM microenvironment is regulated by STAT1 (positive) and STAT3 (negative), and inhibiting the JAK-STAT3 path path represents a new therapeutic option for enhancing CD38 expression and anti-CD38 MoAb-mediated MM cell toxicity.
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