Unique balanced chromosome abnormalities in treatment-related myelodysplastic syndromes and acute myeloid leukemia: report from an international workshop.
A total of 123 balanced rearrangements, including 26 occurring as a sole anomaly, not known to be recurrent in myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) prior to the Workshop, were ascertained retrospectively from 104 patients with treatment-related MDS/AML (t-MDS/t-AML). Thirteen of the aberrations were reported previously in single cases and hence may be classified as recurrent as a result of the Workshop. Patients with Unique aberrations had complex karyotypes more often (P < 0.001 for all pairwise comparisons) than did other Workshop subgroups, with 72% having 3 or more aberrations. Among 85 cases with secondary chromosomal abnormalities, -5, -7, del(5q), and del(7q) were observed in 76%, which is significantly higher (P < or = 0.007 for all pairwise comparisons) than the frequencies found in the Workshop subgroups of patients with previously known recurring aberrations. The chromosome bands most often involved in balanced aberrations were 1p36 and 3q26-27. Treatment exposure was significantly different (less topoisomerase II inhibitor exposure, more radiotherapy-only exposure) than for patients with 11q23 (P < 0.001 and P = 0.002, respectively) and 21q22 (P = 0.007 and P = 0.002, respectively) abnormalities. The median time from the first toxic exposure to secondary disease, 59 months, was significantly longer (P < or = 0.016 for all significant pairwise comparisons) than the median latency of all other patients except those in the Rare subgroup, and the median survival time, 7 months, was significantly shorter than for patients in the 21q22, inv(16), and t(15;17) subgroups (P < or = 0.002 for all pairwise comparisons), but similar to patients in the 11q23 and Rare subgroups. In contrast to known recurring abnormalities, significantly more patients (61%, all P < 0.001) presented with t-MDS, with over one-third of these patients progressing to t-AML. Thus, this group of patients appears to be more similar to the typical t-MDS/t-AML patients, with complex karyotypes as well as chromosome 5 and 7 abnormalities, than to those with recurrent balanced rearrangements.
Olney
Harold J
HJ
Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, USA. hj.olney@umontreal.ca
Mitelman
Felix
F
Johansson
Bertil
B
Mrózek
Krzysztof
K
Berger
Roland
R
Rowley
Janet D
JD
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002869:Chromosome Aberrations / Q000139:chemically induced* / Q000706:statistics & numerical data*; D019457:Chromosome Breakage / Q000235:genetics; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000453:epidemiology*; D013534:Survival; D014178:Translocation, Genetic / Q000187:drug effects / Q000235:genetics