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Adenosine deaminase is an enzyme that breaks down adenosine and deoxyadenosine; blocking it with pentostatin poisons lymphocytes, which is why the drug works in hairy cell leukaemia and some T-cell cancers.
Adenosine deaminase (ADA) converts adenosine to inosine and deoxyadenosine to deoxyinosine in the purine salvage pathway. Lymphocytes depend on it: children born without ADA have severe combined immunodeficiency because deoxyadenosine metabolites accumulate and kill developing lymphocytes. Pentostatin (deoxycoformycin) is a tight-binding ADA inhibitor that reproduces this toxicity on purpose in lymphoid cancers, producing durable remissions in hairy cell leukaemia; it is also used in T-cell leukaemias and lymphomas and in graft-versus-host disease.
In plain words · Adenosine deaminase is an enzyme that breaks down adenosine and deoxyadenosine; blocking it with pentostatin poisons lymphocytes, which is why the drug works in hairy cell leukaemia and some T-cell cancers.
Adenosine deaminase is an enzyme that breaks down adenosine and deoxyadenosine; blocking it with pentostatin poisons lymphocytes, which is why the drug works in hairy cell leukaemia and some T-cell cancers.
ADA is a zinc-dependent hydrolase expressed in most tissues and at high levels in lymphoid cells.
1 product aims at Adenosine deaminase (ADA): small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Lineage antigen shared with normal dendritic cells and monocytes and NK-cells: HPA finds the gene group enriched in that blood lineage, and the 1 medicine aimed at it (Pentostatin) act on the wild-type protein, so the normal lineage is hit too. HPA ADA: RNA group enriched (intestine 454 nTPM, lymphoid tissue 228 nTPM); blood lineage group enriched (dendritic cells 211 nTPM, monocytes 351 nTPM, NK-cells 90 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas ADA tissue; Human Protein Atlas ADA pathology; Open Targets ENSG00000196839 associations
First described 1983. Earliest sequence paper UniProt cites for the protein: Orkin S.H. et al, J. Biol. Chem, 1983, "Molecular cloning of human adenosine deaminase gene sequences". Source.
ADA is a zinc-dependent hydrolase expressed in most tissues and at high levels in lymphoid cells. Inhibiting it raises intracellular deoxyadenosine triphosphate, which blocks ribonucleotide reductase and DNA synthesis and triggers apoptosis, an effect most marked in lymphocytes with high deoxynucleoside kinase activity. Pentostatin binds the enzyme almost irreversibly; cladribine, the other purine analogue used in hairy cell leukaemia, is instead a substrate-resistant deoxyadenosine analogue.
RNA: group enriched (intestine 454 nTPM, lymphoid tissue 228 nTPM), detected in many normal tissues. Blood: group enriched (dendritic cells 211 nTPM, monocytes 351 nTPM, NK-cells 90 nTPM).
No normal tissue stained high; medium in Duodenum, Testis.
No cancer sample stained medium or high.
HPA ADA tissue · HPA ADA pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (purine breakdown, highest in lymphocytes); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
An intravenous drug given every other week that produces long remissions in hairy cell leukaemia by poisoning the leukaemic lymphocytes' purine metabolism; cladribine is the one-week alternative.
Query for this target: (TITLE:"Adenosine deaminase" OR ABSTRACT:"Adenosine deaminase" OR TITLE:"ADA" OR ABSTRACT:"ADA") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Adenosine deaminase (ADA), not a curated reading list.
Shares Pentostatin, Hairy cell leukaemia.
Shares Pentostatin, Chronic lymphocytic leukaemia.
Shares Pentostatin, Hairy cell leukaemia.