Preferred Label : Autologous MGMTP140K Lentiviral Vector-transduced HSCs;
NCIt synonyms : Autologous P140K MGMT-transduced CD34 Cells; Autologous P140K-MGMT transfected HPCs; Autologous P140K MGMT-positive Hematopoietic Stem Cells; Autologous P140K MGMT Hematopoietic Progenitor Cells;
NCIt definition : A preparation of autologous CD34 hematopoietic stem cells (HSCs) transduced with
a lentiviral-based proviral vector encoding for MGMTP140K, a mutant version of the
human DNA repair protein O6-alkylguanine-DNA methyltransferase (MGMT), with potential
protective activity against myelosuppression. MGMTP140K is resistant to the MGMT inhibitor
O6-benzylguanine (O6BG; BG). Upon administration of the autologous MGMTP140K lentiviral
vector-transduced HSCs back into the patient, the HSCs expressing the BG-resistant
mutant MGMT protein could, when used in combination with BG, protect the hematopoietic
system against the hematopoietic toxicity of BG by enabling normal methyltransferase
activity. This protects hematopoiesis and allows for temozolomide (TMZ) and BG chemotherapy
without myelosuppression. MGMT repairs TMZ-induced DNA methylation. The MGMT inhibitor
BG depletes MGMT and thereby maximizes TMZ-mediated anti-tumor response. The depletion
of MGMT in hematopoietic cells leads to unacceptable bone marrow toxicity.;
NCI Metathesaurus CUI : CL1770961;
Origin ID : C182624;
UMLS CUI : C5667674;
Semantic type(s)
- Cell [UMLS semantic type]
- concept_is_in_subset
