# Inherited susceptibility to acute lymphoblastic leukaemia (PAX5, ETV6, IKZF1)

Source: https://onco.cc/terms/germline-all-predisposition/  
OnCo record `germline-all-predisposition` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-11-04
- Also known as: germline ALL predisposition; inherited ALL susceptibility; PAX5 germline; ETV6 germline; IKZF1 germline; familial acute lymphoblastic leukaemia
- Tags: gap-fill; hereditary

## Notes

- NHS England genomic test directory: R366, inherited susceptibility to acute lymphoblastoid leukaemia (ALL), panel PAX5 and ETV6.

## Sources

- Maese, Clin Cancer Res 2024: surveillance for children with predisposition to haematopoietic malignancy (AACR update): https://doi.org/10.1158/1078-0432.ccr-24-0685
- NHS England National Genomic Test Directory, rare and inherited disease, version 9 (spreadsheet): https://www.england.nhs.uk/wp-content/uploads/2018/08/rare-and-inherited-disease-national-genomics-test-directory-v9.xlsx

## Connected records

- terms: [Ataxia-telangiectasia](https://onco.cc/terms/ataxia-telangiectasia/), [Bloom syndrome](https://onco.cc/terms/bloom-syndrome/), [Constitutional mismatch repair deficiency (CMMRD)](https://onco.cc/terms/constitutional-mismatch-repair-deficiency/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [ETV6](https://onco.cc/targets/etv6/), [PAX5](https://onco.cc/targets/pax5/)

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