PMID- 12200689
OWN - NLM
STAT- MEDLINE
DCOM- 20020926
LR  - 20130304
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 16
IP  - 9
DP  - 2002 Sep
TI  - Incidence and significance of cryptic chromosome aberrations detected by 
      fluorescence in situ hybridization in acute myeloid leukemia with normal 
      karyotype.
PG  - 1745-51
AB  - To better define the incidence and significance of cryptic chromosome lesions in 
      acute myeloid leukemia (AML), fluorescence in situ hybridization (FISH) studies 
      were performed in interphase cells and, when appropriate, in metaphase cells and 
      in morphologically intact BM smears. Fifty-five adult de novo AML (group A) and 
      27 elderly AML or AML after myelodysplastic syndrome (AML-MDS) (group B) were 
      tested using probes detecting the following anomalies: -5, -7, +8, deletions of 
      5q31, 7q31, 12p13/ETV6, 17p13/p53, 20q11. All the patients had a normal karyotype 
      in more than 20 cells and tested negative for the common AML-associated fusion 
      genes. No patient in group A was found to carry occult chromosome anomalies, 
      whereas 8/27 patients in group B (P < 0.0001) showed 5q31 or 7q31 deletion (three 
      cases each), a 17p13/p53deletion or trisomy 8 (one case each) in 33-60% 
      interphase cells. Metaphase cells showed only one hybridization signal at 5q31 
      (three cases) and 7q31 (one case), whereas two normal signals at 7q31 and 
      chromosome 8 centromeres were seen in two patients with 7q deletion and trisomy 8 
      in interphase cells. The majority of blast cells (76-94%) carried the chromosome 
      anomaly in all cases; erythroid involvement in a minority of cells was seen in 
      three patients. In group B, the presence of occult chromosome anomalies was 
      associated with exposure to myelotoxic agents in the workplace (5/8 cases vs 
      3/19, P = 0.026) and with a lower complete remission rate (0/6 patients vs 7/12, 
      P = 0.024). We arrived at the following conclusions: (1) cryptic chromosome 
      deletions in the order of a few hundred kb magnitude may be found in a fraction 
      of elderly AML or MDS-related AML and not in de novo adult AML with normal 
      karyotype; (2) these chromosome lesions are usually represented by submicroscopic 
      rearrangements; (3) they display a specific pattern of cell-lineage involvement 
      arguing in favor of their role in the outgrowth of the leukemic blast cells; (4) 
      they are associated with a history of exposure to myelotoxic agents in the 
      workplace and, possibly, with resistance to induction treatment.
FAU - Cuneo, A
AU  - Cuneo A
AD  - Dipartimento di Scienze Biomediche e Terapie Avanzate - Sezione di Ematologia, 
      University of Ferrara, Italy.
FAU - Bigoni, R
AU  - Bigoni R
FAU - Cavazzini, F
AU  - Cavazzini F
FAU - Bardi, A
AU  - Bardi A
FAU - Roberti, M G
AU  - Roberti MG
FAU - Agostini, P
AU  - Agostini P
FAU - Tammiso, E
AU  - Tammiso E
FAU - Ciccone, N
AU  - Ciccone N
FAU - Mancini, M
AU  - Mancini M
FAU - Nanni, M
AU  - Nanni M
FAU - De Cuia, R
AU  - De Cuia R
FAU - Divona, M
AU  - Divona M
FAU - La Starza, R
AU  - La Starza R
FAU - Crescenzi, B
AU  - Crescenzi B
FAU - Testoni, N
AU  - Testoni N
FAU - Rege Cambrin, G
AU  - Rege Cambrin G
FAU - Mecucci, C
AU  - Mecucci C
FAU - Lo Coco, F
AU  - Lo Coco F
FAU - Saglio, G
AU  - Saglio G
FAU - Castoldi, G
AU  - Castoldi G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
SB  - IM
MH  - Acute Disease
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Bone Marrow/pathology
MH  - Cell Lineage/*genetics
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 7/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Myeloid/*genetics/pathology
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/*genetics/pathology
MH  - Trisomy/diagnosis
EDAT- 2002/08/30 10:00
MHDA- 2002/09/27 06:00
CRDT- 2002/08/30 10:00
PHST- 2002/01/21 00:00 [received]
PHST- 2002/04/17 00:00 [accepted]
PHST- 2002/08/30 10:00 [pubmed]
PHST- 2002/09/27 06:00 [medline]
PHST- 2002/08/30 10:00 [entrez]
AID - 10.1038/sj.leu.2402605 [doi]
PST - ppublish
SO  - Leukemia. 2002 Sep;16(9):1745-51. doi: 10.1038/sj.leu.2402605.