{"entity":{"id":"germline-all-predisposition","kind":"term","name":"Inherited susceptibility to acute lymphoblastic leukaemia (PAX5, ETV6, IKZF1)","aka":["germline ALL predisposition","inherited ALL susceptibility","PAX5 germline","ETV6 germline","IKZF1 germline","familial acute lymphoblastic leukaemia"],"tldr":"A small share of children with acute lymphoblastic leukaemia were born with a gene change, in genes such as PAX5, ETV6 or IKZF1, that raised their risk. Finding it guides follow-up, testing of brothers and sisters, and the choice of a family stem cell donor.","summary":"AACR 2024 groups PAX5-associated predisposition to ALL and IKAROS (IKZF1)-associated predisposition with the conditions that do not carry a risk of MDS: routine blood tests are not needed without symptoms or abnormal examination, and an annual examination and education about symptoms are advised. ETV6-associated predisposition to myeloid or lymphoid neoplasms is grouped with those that do: blood count every 6 to 12 months and bone marrow every one to three years. For IKZF1, about 1% of children with B-cell ALL carry a germline pathogenic variant, cumulative malignancy incidence is about 10% by 20, and immune deficiency or dysregulation appears in about 65 to 70% of carriers. Li-Fraumeni syndrome, constitutional mismatch repair deficiency, Down syndrome, ataxia-telangiectasia, Nijmegen breakage syndrome and Bloom syndrome also carry a predisposition to lymphoid neoplasms.","asOf":"2026-11-04","links":[{"label":"Maese, Clin Cancer Res 2024: surveillance for children with predisposition to haematopoietic malignancy (AACR update)","url":"https://doi.org/10.1158/1078-0432.ccr-24-0685"},{"label":"NHS England National Genomic Test Directory, rare and inherited disease, version 9 (spreadsheet)","url":"https://www.england.nhs.uk/wp-content/uploads/2018/08/rare-and-inherited-disease-national-genomics-test-directory-v9.xlsx"}],"tags":["gap-fill","hereditary"],"related":["ataxia-telangiectasia","bloom-syndrome","constitutional-mismatch-repair-deficiency"],"cancers":["all-leukemia"],"sections":[],"technologies":["germline-testing"],"targets":["pax5","etv6"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hereditary-cancer-syndromes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["NHS England genomic test directory: R366, inherited susceptibility to acute lymphoblastoid leukaemia (ALL), panel PAX5 and ETV6."],"category":"Genomics & genetics"},"route":"/terms/germline-all-predisposition/","neighbours":{"term":[{"id":"ataxia-telangiectasia","kind":"term","name":"Ataxia-telangiectasia","route":"/terms/ataxia-telangiectasia/"},{"id":"bloom-syndrome","kind":"term","name":"Bloom syndrome","route":"/terms/bloom-syndrome/"},{"id":"constitutional-mismatch-repair-deficiency","kind":"term","name":"Constitutional mismatch repair deficiency (CMMRD)","route":"/terms/constitutional-mismatch-repair-deficiency/"},{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"target":[{"id":"etv6","kind":"target","name":"ETV6","route":"/targets/etv6/"},{"id":"pax5","kind":"target","name":"PAX5","route":"/targets/pax5/"}]}}