PMID- 20417871
OWN - NLM
STAT- MEDLINE
DCOM- 20100504
LR  - 20151119
IS  - 1873-4456 (Electronic)
IS  - 0165-4608 (Linking)
VI  - 199
IP  - 1
DP  - 2010 May
TI  - Clonal evolution with double Ph followed by tetraploidy in imatinib-treated 
      chronic myeloid leukemia with e19a2 transcript in transformation.
PG  - 56-61
LID - 10.1016/j.cancergencyto.2010.01.018 [doi]
AB  - Chronic myeloid leukemia (CML) with the e19a2 transcript coding for p230 is 
      typically associated with a benign clinical course unless accompanied at 
      presentation with additional chromosomal abnormalities. We report here a case of 
      CML with e19a2 who did not show additional chromosomal abnormalities at 
      diagnosis, but progressed to the fatal advanced stage in approximately 2 years. 
      The patient was initially treated with imatinib, which, however, could be 
      administered only intermittently at reduced doses because of recurrent 
      thrombocytopenia and fluid retention. Nine months after starting imatinib, 
      fluorescence in situ hybridization (FISH) with the BCR/ABL-ES fusion probe 
      revealed 96% and 3% of bone marrow cells with one and two BCR/ABL1 fusion 
      signals, respectively. Two years after starting therapy, leukocytosis recurred 
      and the bone marrow contained 8.2% large and bizarre myeloblasts. Cytogenetic 
      analysis revealed double Ph clones as well as tetraploid cells with four to five 
      Ph chromosomes. FISH analysis confirmed the presence of cells with two to five 
      BCR/ABL1 fusion signals. The patient died of disease progression in 2 months. No 
      point mutation was detected in the region coding for the BCR/ABL tyrosine kinase 
      domain by sequence analysis. It is speculated that the amplification of the 
      BCR/ABL1 fusion gene by duplication of Ph and tetraploidy led to the progression 
      of CML with the e19a2 transcript.
CI  - 2010 Elsevier Inc. All rights reserved.
FAU - Oshikawa, Gaku
AU  - Oshikawa G
AD  - Department of Hematology, Tokyo Medical and Dental University, Bunkyoku, Japan.
FAU - Kurosu, Tetsuya
AU  - Kurosu T
FAU - Arai, Ayako
AU  - Arai A
FAU - Murakami, Naomi
AU  - Murakami N
FAU - Miura, Osamu
AU  - Miura O
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (abl-bcr fusion protein, human)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Base Sequence
MH  - Benzamides
MH  - Bone Marrow/pathology
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Clone Cells
MH  - DNA Mutational Analysis
MH  - Female
MH  - Fusion Proteins, bcr-abl/*genetics/metabolism
MH  - Gene Expression Regulation, Leukemic
MH  - Humans
MH  - Imatinib Mesylate
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/*genetics
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - *Philadelphia Chromosome
MH  - Piperazines/*therapeutic use
MH  - *Polyploidy
MH  - Pyrimidines/*therapeutic use
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Neoplasm/analysis/*genetics
MH  - Time Factors
EDAT- 2010/04/27 06:00
MHDA- 2010/05/05 06:00
CRDT- 2010/04/27 06:00
PHST- 2009/07/22 00:00 [received]
PHST- 2010/01/22 00:00 [revised]
PHST- 2010/01/25 00:00 [accepted]
PHST- 2010/04/27 06:00 [entrez]
PHST- 2010/04/27 06:00 [pubmed]
PHST- 2010/05/05 06:00 [medline]
AID - S0165-4608(10)00045-2 [pii]
AID - 10.1016/j.cancergencyto.2010.01.018 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2010 May;199(1):56-61. doi: 
      10.1016/j.cancergencyto.2010.01.018.