PMID- 21739181
OWN - NLM
STAT- MEDLINE
DCOM- 20111027
LR  - 20211020
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Linking)
VI  - 137
IP  - 9
DP  - 2011 Sep
TI  - Molecular cytogenetic characterization of Philadelphia-negative rearrangements in 
      chronic myeloid leukemia patients.
PG  - 1329-36
LID - 10.1007/s00432-011-1002-4 [doi]
AB  - BACKGROUND: The BCR/ABL gene rearrangement is generated by a reciprocal 
      translocation t(9;22)(q34;q11) in chronic myeloid leukemia (CML) patients. In 
      most cases, it is cytogenetically visualized by the Philadelphia (Ph) chromosome. 
      About 5-10% of CML patients lack cytogenetic evidence of the Ph translocation but 
      show BCR/ABL fusion by fluorescence in situ hybridization (FISH) or reverse 
      transcriptase-polymerase chain reaction (RT-PCR). Deletions around the 
      breakpoints on derivative chromosome 9 including 5'ABL and 3'BCR sequences occur 
      in 10-15% of Ph-positive CML patients and are thought to have prognostic 
      significance. METHODS: We explored cryptic rearrangements involving chromosomes 9 
      and 22 in 3 CML patients with an apparently normal bone marrow karyotypes using 
      multiplex RT-PCR and FISH with commercial and home-brew probes. RESULTS: The 
      BCR/ABL fusion transcripts were detected by RT-PCR. Using commercial FISH probes, 
      the BCR/ABL fusion gene was found on chromosome 22 in two patients and on 
      chromosome 9 in one patient. Consecutive FISH assays clarified the mechanism of 
      the masked Ph chromosome: in the 3 patients, Ph rearrangement resulted from 
      double mechanism consisting in standard translocation t(9;22)(q34;q11) followed 
      by a second reversed translocation t(9;22)(q34;q11). One patient achieved major 
      cytogenetic response after 6 months of imatinib therapy, and one patient had 
      successful bone marrow transplant. CONCLUSIONS: In this study, we have 
      characterized three Ph-negative CML patients with cryptic BCR/ABL rearrangement 
      generated after an uncommon mechanism involving two sequential translocations and 
      confirm that the BCR/ABL hybrid gene may be located on other sites than 22q11. 
      Ph-negative CML patients with BCR/ABL fusion gene have the same prognosis as 
      patients with classical t(9;22).
FAU - Bennour, Ayda
AU  - Bennour A
AD  - Department of Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat 
      Hached University Teaching Hospital, Sousse, Tunisia. aydabennour@yahoo.fr
FAU - Bellaaj, Hatem
AU  - Bellaaj H
FAU - Ben Youssef, Yosra
AU  - Ben Youssef Y
FAU - Elloumi, Moez
AU  - Elloumi M
FAU - Khelif, Abderrahim
AU  - Khelif A
FAU - Saad, Ali
AU  - Saad A
FAU - Sennana, Halima
AU  - Sennana H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110708
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Chromosome Banding
MH  - Chromosomes, Human, Pair 22/genetics
MH  - Chromosomes, Human, Pair 9/genetics
MH  - Cohort Studies
MH  - *Cytogenetics/methods
MH  - Early Detection of Cancer
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/*genetics
MH  - Male
MH  - Middle Aged
MH  - Philadelphia Chromosome
MH  - Translocation, Genetic
EDAT- 2011/07/09 06:00
MHDA- 2011/10/28 06:00
CRDT- 2011/07/09 06:00
PHST- 2011/05/06 00:00 [received]
PHST- 2011/06/27 00:00 [accepted]
PHST- 2011/07/09 06:00 [entrez]
PHST- 2011/07/09 06:00 [pubmed]
PHST- 2011/10/28 06:00 [medline]
AID - 10.1007/s00432-011-1002-4 [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2011 Sep;137(9):1329-36. doi: 10.1007/s00432-011-1002-4. 
      Epub 2011 Jul 8.