PMID- 12764379
OWN - NLM
STAT- MEDLINE
DCOM- 20030708
LR  - 20131121
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 17
IP  - 6
DP  - 2003 Jun
TI  - Patterns of BCR/ABL gene rearrangements by interphase fluorescence in situ 
      hybridization (FISH) in BCR/ABL+ leukemias: incidence and underlying genetic 
      abnormalities.
PG  - 1124-9
AB  - Interphase fluorescence in situ hybridization (iFISH) is increasingly used for 
      the identification of BCR/ABL gene rearrangements in chronic myeloid leukemia 
      (CML) and acute lymphoblastic leukemia (ALL). In the present study, we have 
      explored the incidence of both typical and atypical iFISH patterns of BCR/ABL 
      gene rearrangements in a series of 168 consecutive BCR/ABL+ patients--135 CML, 31 
      precursor B-ALL and two acute myeloblastic leukemia (AML) cases--and established 
      their underlying genetic alterations through further molecular and chromosome 
      analyses. Two different FISH probes (Vysis Inc., Downers Grove, IL, USA) were 
      used: the LSI BCR/ABL dual color extra signal (ES) and the dual color dual fusion 
      BCR/ABL probe (D-FISH). Our results show that most BCR/ABL+ patients (83%, 
      including 88% of all CML, 61% of ALL and one of two AML) displayed typical iFISH 
      patterns of either Major (M) BCR/ABL (87% of CML, 13% of ALL and one of the two 
      AML) or minor (m) BCR/ABL gene rearrangements (1% of all CML and 48% of ALL 
      cases) with the two probes. Further molecular and cytogenetic studies confirmed 
      the presence of such typical rearrangements in all except one of these ALL cases 
      who had coexistence of an MBCR/ABL and an mBCR/ABL gene rearrangement together 
      with monosomy 9. In the remaining 29 cases (17%), up to five different atypical 
      iFISH patterns were detected with the ES probe. Atypical iFISH patterns were most 
      frequently due to additional numerical changes--most often supernumerary 
      Philadelphia (Ph) chromosome (7%) but also gain or loss of chromosome 9 (1%) or 
      22 (1%). Deletion of 9q sequences proximal to the breakpoint were also frequently 
      observed with the ES probe (8%). Application of the D-FISH probe showed that in 
      most of these latter cases (5%) deletion of 22q sequences distal to the 
      breakpoint also occurred. The remaining cases with atypical iFISH had cryptic 
      insertion of BCR in 9q34 (1%). Exact interpretation of each iFISH pattern was 
      supported by FISH on metaphases and molecular determination of the BCR 
      breakpoint. In summary, our results indicate that despite the high incidence of 
      typical iFISH patterns of BCR/ABL gene rearrangements, atypical patterns are also 
      found in BCR/ABL+ acute leukemias; the precise definition of the alteration 
      present in individual cases is dependent on metaphase studies and molecular 
      definition of the breakpoint.
FAU - Primo, D
AU  - Primo D
AD  - Servicio General de Citometria, Spain.
FAU - Tabernero, M D
AU  - Tabernero MD
FAU - Rasillo, A
AU  - Rasillo A
FAU - Sayagues, J M
AU  - Sayagues JM
FAU - Espinosa, A B
AU  - Espinosa AB
FAU - Chillon, M C
AU  - Chillon MC
FAU - Garcia-Sanz, R
AU  - Garcia-Sanz R
FAU - Gutierrez, N
AU  - Gutierrez N
FAU - Giralt, M
AU  - Giralt M
FAU - Hagemeijer, A
AU  - Hagemeijer A
FAU - San Miguel, J F
AU  - San Miguel JF
FAU - Orfao, A
AU  - Orfao A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
CIN - Leukemia. 2004 Jan;18(1):161-2; author reply 162-4. PMID: 14603334
MH  - Bone Marrow/pathology
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 22/genetics
MH  - Chromosomes, Human, Pair 9/genetics
MH  - Fusion Proteins, bcr-abl/*genetics
MH  - Gene Deletion
MH  - *Gene Rearrangement
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Incidence
MH  - Interphase
MH  - Karyotyping
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics
MH  - Monosomy
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics
EDAT- 2003/05/24 05:00
MHDA- 2003/07/09 05:00
CRDT- 2003/05/24 05:00
PHST- 2003/05/24 05:00 [pubmed]
PHST- 2003/07/09 05:00 [medline]
PHST- 2003/05/24 05:00 [entrez]
AID - 2402963 [pii]
AID - 10.1038/sj.leu.2402963 [doi]
PST - ppublish
SO  - Leukemia. 2003 Jun;17(6):1124-9. doi: 10.1038/sj.leu.2402963.