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PARP inhibitors, platinum, and radioligand drugs can push pre-existing blood-cell clones toward leukaemia in a few patients. Predicting who could let us choose therapies more safely.
This open question asks which patients' blood clones will become leukaemia after treatment: PARP inhibitors, platinum and radioligand drugs push pre-existing clones toward leukaemia in a few patients. Therapy-related myeloid neoplasms follow PPM1D and TP53 clonal haematopoiesis; incidence after PARP inhibitors is low but rising with longer use and Radioligand therapy (beta emitters), see Clonal haematopoiesis (CHIP). The hypothesis is that baseline CHIP genotype and variant allele fraction, with the planned genotoxic exposure, predict therapy-related MDS and AML well enough to guide drug choice and monitoring (Bolton 2020). The test is a prospective registry with baseline CHIP sequencing before these therapies, relevant to Acute myeloid leukaemia, Ovarian cancer and Prostate cancer.
Many older people carry blood clones one or two steps from leukaemia, and those clones also drive heart disease through inflammation. CHIP is why blood-based cancer tests must filter out mutations from blood cells, and it opens a route to preventing both leukaemia and cardiovascular events in carriers.
This paper is the reason TP53 status, MDM2 amplification and CDKN2A loss are read together in tumour genomes. It frames the current drug development around MDM2 inhibitors and mutant p53 reactivators as attempts to restore a network rather than a single protein.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, Memorial Sloan Kettering Cancer Center, TP53, Ovarian cancer and the tags mechanism, open-question.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, TP53 and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center, Prostate cancer and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center, Acute myeloid leukaemia and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center, Ovarian cancer and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center, Prostate cancer and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.