Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype.
OBJECTIVE
To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML).


METHODS
Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years.


RESULTS
Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities. Among the latter subgroup, loss of a single chromosome (n = 109) conferred negative prognostic impact (4-year OS, 12%; poor outcome). Loss of chromosome 7 was most common, but outcome of AML patients with single monosomy -7 (n = 63; 4-year OS, 13%) and other single autosomal monosomies (n = 46; 4-year OS, 12%) did not differ. Structural chromosomal abnormalities influenced prognosis only in association with a single autosomal monosomy (4-year OS, 4% for very poor v 24% for poor). We derived a monosomal karyotype (MK) as a predictor for very poor prognosis of AML that refers to two or more distinct autosomal chromosome monosomies (n = 116; 4-year OS, 3%) or one single autosomal monosomy in the presence of structural abnormalities (n = 68; 4-year OS, 4%). In direct comparisons, MK provides significantly better prognostic prediction than the traditionally defined complex karyotype, which considers any three or more or five or more clonal cytogenetic abnormalities, and also than various individual specific cytogenetic abnormalities (eg, del[5q], inv[3]/t[3;3]) associated with very poor outcome.


CONCLUSIONS
MK enables (in addition to CN and CBF) the prognostic classification of two new aggregates of cytogenetically abnormal AML, the unfavorable risk MK-negative category (4-year OS, 26% +/- 2%) and the highly unfavorable risk MK-positive category (4-year OS, 4% +/- 1%).
Breems
Dimitri A
DA
Department of Hematology, Hospital Network Antwerp, Campus Stuivenberg, Antwerp, Belgium.
Van Putten
Wim L J
WL
De Greef
Georgine E
GE
Van Zelderen-Bhola
Shama L
SL
Gerssen-Schoorl
Klasien B J
KB
Mellink
Clemens H M
CH
Nieuwint
Aggie
A
Jotterand
Martine
M
Hagemeijer
Anne
A
Beverloo
H Berna
HB
Löwenberg
Bob
B
D000293:Adolescent; D000328:Adult; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis