Isodicentric 7p, idic(7)(q11.2), in acute myeloid leukemia associated with older age and favorable response to induction chemotherapy: a new clinical entity?
Three adult de novo acute myeloid leukemias (AML M1, M2, and M4) with an isochromosome 7p are presented. No additional abnormalities were detected by G-band and multicolor, using combined binary ratio labeling, fluorescence in situ hybridization (FISH) analyses, indicating that the i(7p) was the sole, i.e., the primary, chromosomal aberration. Although the patients were elderly--68, 72, and 78 years old--they all responded very well to chemotherapy, achieving complete remission lasting more than a year. Further FISH analyses, using painting, centromeric, as well as 7q11.2-specific YAC probes, revealed that the i(7p) contained two centromeres and that the breakpoints were located in 7q11.2. Thus, the abnormality should formally be designated idic(7)(q11.2). The detailed mapping disclosed a breakpoint heterogeneity, with the breaks in 7q11.2 varying among the cases, being at least 1,310 kb apart. Furthermore, the breakpoints also differed within one of the cases, being located on both the proximal and the distal side of the most centromeric probe used. Based on our three patients, as well as on a previously reported 82-year-old patient with AML M2 and idic(7)(q11) as the only chromosomal change, we suggest that this abnormality, as the sole anomaly, is associated with AML in elderly patients who display a good response to induction chemotherapy and, hence, have a favorable prognosis. Furthermore, the heterogeneous breakpoints in 7q11.2 suggest that the important functional outcome of the idic(7)(q11.2) is the genomic imbalance incurred, i.e., gain of 7p and loss of 7q material, rather than a rearrangement of a specific gene.
Johansson
B
B
Department of Clinical Genetics, Lund University Hospital, Sweden. bertil.johansson@klingen.lu.se
Axelsson
P
P
Billström
R
R
Strömbeck
B
B
Arheden
K
K
Olofsson
T
T
Cervin
A
A
Adriansson
M
M
Tanke
H J
HJ
Mitelman
F
F
Fioretos
T
T
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002871:Chromosome Banding; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D018404:Isochromosomes / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000235:genetics; D008297:Male; D012074:Remission Induction; D013866:Thioguanine / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D013866:Thioguanine; D015255:Idarubicin