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Losing a piece of the long arm of chromosome 5 causes a distinctive low-risk myelodysplastic syndrome, typically an older woman with severe anaemia and a normal or high platelet count; it is the one MDS with a drug matched to its genetics, lenalidomide, which makes two-thirds of patients transfusion-free unless TP53 is also mutated.
What is measured: an interstitial deletion of the long arm of chromosome 5. How: marrow karyotype (G-banding) and FISH with 5q31 or 5q33 probes (EGR1, CSF1R) at diagnosis and in follow-up; WHO 2022 defines MDS with low blasts and isolated 5q deletion, allowing one additional abnormality other than monosomy 7 or del(7q); the marrow shows hypolobated megakaryocytes; TP53 is sequenced because a subclonal mutation, present in about a fifth at diagnosis, predicts lenalidomide failure and progression; the deletion counts as a good-risk cytogenetic category in IPSS-R. Mechanism: haploinsufficiency of RPS14 (anaemia), CSNK1A1 (lenalidomide degrades casein kinase 1 alpha through cereblon and so kills the clone selectively) and the miR-145/146a locus (thrombocytosis). What a result changes: transfusion-dependent anaemia in lower-risk del(5q) MDS is treated with lenalidomide 10 mg (MDS-003 and MDS-004: transfusion independence in 56 to 67 percent, with cytogenetic responses), dose-adjusted for the neutropenia and thrombocytopenia it causes; a TP53 mutation weakens the response and pushes towards hypomethylating agents or transplant; in other lower-risk MDS the drug helps only about a quarter; progression to AML (10 to 20 percent) is watched for. Where it matters: lower-risk MDS, and higher-risk MDS when del(5q) sits within a complex karyotype.
Shares IPSS-R and IPSS-M (myelodysplastic syndrome risk scores), TP53-mutated (p53-abnormal), Cytogenetics and karyotype.
Shares IPSS-R and IPSS-M (myelodysplastic syndrome risk scores), Luspatercept, Lower-risk myelodysplastic syndromes.
Shares TP53-mutated (p53-abnormal), Cytogenetics and karyotype.
Shares TP53-mutated (p53-abnormal), FISH / ISH (in situ hybridisation).
Shares Lower-risk myelodysplastic syndromes, Cytogenetics and karyotype, Higher-risk myelodysplastic syndromes.