Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12.
OBJECTIVE
Karyotype is an independent indicator of prognosis in acute myeloid leukemia (AML) that is widely applied to risk-adapted therapy. Because AML is rare in children, the true prognostic significance of individual chromosomal abnormalities in this age group remains unclear.


METHODS
This cytogenetic study of 729 childhood patients classified them into 22 subgroups and evaluated their incidence and risk.


RESULTS
Rearrangements of 11q23 were the most frequent abnormality found in approximately 16% of patients, with 50% of these in infants. The outcome for all patients with 11q23 abnormalities was intermediate; no difference was observed for those with t(9;11)(p21-22;q23). The core binding factor leukemias with the translocations t(8;21)(q22;q22) and inv(16)(p13q22) occurred at incidences of 14% and 7%, respectively, predominantly in older children, and their prognosis was favorable. An adverse outcome was observed in patients with monosomy 7, abnormalities of 5q, and t(6;9)(p23;q34). Abnormalities of 3q and complex karyotypes, in the absence of favorable-risk features, have been associated with an adverse outcome in adults, but the results were not significant in this childhood series. However, the presence of 12p abnormalities predicted a poor outcome.


CONCLUSIONS
Because the spectrum of chromosomal changes and their risk association seem to differ between children and adults with AML, biologic differences are emerging, which will contribute to the redefinition of risk stratification for different age groups in the future.
Harrison
Christine J
CJ
Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Queen Victoria Road, Newcastle-upon-Tyne, UK. christine.harrison@newcastle.ac.uk
Hills
Robert K
RK
Moorman
Anthony V
AV
Grimwade
David J
DJ
Hann
Ian
I
Webb
David K H
DK
Wheatley
Keith
K
de Graaf
Siebold S N
SS
van den Berg
Eva
E
Burnett
Alan K
AK
Gibson
Brenda E S
BE
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10; D002881:Chromosomes, Human, Pair 12; D016001:Confidence Intervals; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D005260:Female; D005453:Fluorescence; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom