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Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with  KMT2A-AFF1 , complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% &amp; 53% and correspondingly poor survival. Patients with  BCR-ABL1  had an outcome similar to other patients. JAK-STAT abnormalities ( CRLF2 ,  JAK2 ) occurred in 6% patients and were associated with a high relapse rate (56%). Patients with ABL-class fusions were rare (1%). A small group of patients with  ZNF384  fusions ( n  = 12) had very good survival. CNA affecting  IKZF1, CDKN2A/B, PAX5, BTG1, ETV6, EBF1, RB1  and PAR1 were assessed in 436 patients. None of the individual deletions or profiles were associated with survival, either in the cohort overall or within key subgroups. Collectively these data indicate that primary genetic abnormalities are stronger prognostic markers than secondary deletions. We propose a revised UKALL genetic risk classification based on key established chromosomal abnormalities: (1) very high risk: CK, HoTr or JAK-STAT abnormalities; (2) high risk:  KMT2A  fusions; (3) Tyrosine kinase activating:  BCR-ABL1  and ABL-class fusions; (4) standard risk: all other patients.

Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study