PMID- 9790503
OWN - NLM
STAT- MEDLINE
DCOM- 19990524
LR  - 20191024
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 23
IP  - 3
DP  - 1998 Nov
TI  - Establishment of a cell line with variant BCR/ABL breakpoint expressing 
      P180BCR/ABL from late-appearing Philadelphia-positive acute biphenotypic 
      leukemia.
PG  - 227-38
AB  - In acute leukemia (AL) with a late-appearing Philadelphia (la-Ph) translocation, 
      it is unclear whether these translocations arise from the same molecular event as 
      classical Ph translocations. In order to elucidate the molecular events of la-Ph 
      and subsequent translocations of la-Ph leukemia, we performed molecular analysis 
      on the complex rearrangements, in a cell line, MY, which was established from 
      bone marrow mononuclear cells of a patient with a la-Ph acute biphenotypic 
      leukemia. This la-Ph, expressing an acute lymphoblastic leukemia (ALL)-type 
      BCR/ABL transcript, produces a novel P180BCR/ABL fusion protein reflecting 
      deletion of 174 bases (58 amino acids) encoded by the a2 exon of the ABL gene. An 
      immune complex kinase assay showed that this protein had autophosphorylation 
      activity. Fluorescence in situ hybridization (FISH) in conjunction with G-banding 
      analysis revealed that the initial der(9)t(9;22)(q34;q11) progressed to a 
      der(9)(9pter-->9q34::22q11-->22q13::5q11.2 -->5q15:: 10q23-->10qter) by, first, a 
      three-way translocation among the der(9)t(9;22)(q34;q11), chromosome 5, and the 
      normal chromosome 22, and then a subsequent translocation with chromosome 10. 
      Moreover, both the end-stage leukemic cells of the patient and the MY cell line 
      had another translocation, t(X;12)(p11.2;p13). The 12p breakpoint was located 
      near the ETV6 gene by analysis of pulsed-field gel electrophoresis, but 
      transcription of ETV6 was unaffected. Tumorigenicity analysis indicated that an 
      additional translocation, t(2;3)(p16;q29), may have caused a more malignant 
      clone, because only MY cells with the t(2;3)(p16;q29) were capable of growing 
      subcutaneously in nude mice within 40 days. The molecular events of 
      leukemogenesis and leukemic progression in the present la-Ph AL occurred by 
      accumulation of unique translocations. This cell line, MY, expressing a novel 
      variant P180BCR/ABL protein with a deletion of the a2 exon of the ABL gene, may 
      be useful for elucidating the pathophysiology of this fusion protein and for 
      studying ETV6-related leukemogenesis and t(2;3), as well as the molecular 
      mechanisms of the complex translocations.
FAU - Inokuchi, K
AU  - Inokuchi K
AD  - Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
FAU - Shinohara, T
AU  - Shinohara T
FAU - Futaki, M
AU  - Futaki M
FAU - Hanawa, H
AU  - Hanawa H
FAU - Tanosaki, S
AU  - Tanosaki S
FAU - Yamaguchi, H
AU  - Yamaguchi H
FAU - Nomura, T
AU  - Nomura T
FAU - Dan, K
AU  - Dan K
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - EC 2.7.11.1 (BCR protein, human)
RN  - EC 2.7.11.1 (Bcr protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Cells/pathology
MH  - Bone Marrow Transplantation
MH  - Cell Culture Techniques/methods
MH  - Electrophoresis, Gel, Pulsed-Field
MH  - Female
MH  - Fusion Proteins, bcr-abl/*genetics/metabolism
MH  - Genes, abl/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - K562 Cells
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology/*genetics/*pathology
MH  - Mice
MH  - Mice, Nude
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Oncogene Proteins/genetics
MH  - *Protein-Tyrosine Kinases
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-bcr
MH  - Tumor Cells, Cultured
EDAT- 1998/10/28 03:03
MHDA- 2000/06/20 09:00
CRDT- 1998/10/28 03:03
PHST- 1998/10/28 03:03 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/10/28 03:03 [entrez]
AID - 10.1002/(SICI)1098-2264(199811)23:3<227::AID-GCC4>3.0.CO;2-3 [pii]
AID - 10.1002/(sici)1098-2264(199811)23:3<227::aid-gcc4>3.0.co;2-3 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 1998 Nov;23(3):227-38. doi: 
      10.1002/(sici)1098-2264(199811)23:3<227::aid-gcc4>3.0.co;2-3.