Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children’s Oncology Group

Hoff FW, Qiu Y, Brown BD, Gerbing RB, Leonti AR, Ries RE, Gamis AS, Aplenc R, Kolb EA, Alonzo TA, Meshinchi S, Jenkins GN, Horton TM, Kornblau SM. Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children’s Oncology Group. Proteomics Clin Appl. 2023 Nov;17(6):e2200109. doi: 10.1002/prca.202200109. Epub 2023 Jun 7. PubMed PMID: 37287368; PubMed Central PMCID: PMC10700663.

The endoplasmic reticulum (ER) is the major site of protein synthesis and folding in the cell. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the main mechanisms of ER-mediated cell stress adaptation. Targeting the cell stress response is a promising therapeutic approach in acute myeloid leukemia (AML). Protein expression levels of VCP, a chief element of ERAD, were measured in peripheral blood samples from in 483 pediatric AML patients using reverse phase protein array methodology. Patients participated in the Children’s Oncology Group AAML1031 phase 3 clinical trial that randomized patients to standard chemotherapy (cytarabine (Ara-C), daunorubicin, and etoposide [ADE]) vs ADE plus bortezomib (ADE+BTZ).