Linked Life Data

9790503

Source:http://linkedlifedata.com/resource/pubmed/id/9790503

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-5-24
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1045-2257
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
227-38
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9790503-Amino Acid Sequence, pubmed-meshheading:9790503-Animals, pubmed-meshheading:9790503-Base Sequence, pubmed-meshheading:9790503-Bone Marrow Cells, pubmed-meshheading:9790503-Bone Marrow Transplantation, pubmed-meshheading:9790503-Cell Culture Techniques, pubmed-meshheading:9790503-Electrophoresis, Gel, Pulsed-Field, pubmed-meshheading:9790503-Female, pubmed-meshheading:9790503-Fusion Proteins, bcr-abl, pubmed-meshheading:9790503-Genes, abl, pubmed-meshheading:9790503-Humans, pubmed-meshheading:9790503-In Situ Hybridization, Fluorescence, pubmed-meshheading:9790503-K562 Cells, pubmed-meshheading:9790503-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:9790503-Mice, pubmed-meshheading:9790503-Mice, Nude, pubmed-meshheading:9790503-Middle Aged, pubmed-meshheading:9790503-Molecular Sequence Data, pubmed-meshheading:9790503-Oncogene Proteins, pubmed-meshheading:9790503-Protein-Tyrosine Kinases, pubmed-meshheading:9790503-Proto-Oncogene Proteins, pubmed-meshheading:9790503-Proto-Oncogene Proteins c-bcr, pubmed-meshheading:9790503-Tumor Cells, Cultured
pubmed:year
1998
pubmed:articleTitle
Establishment of a cell line with variant BCR/ABL breakpoint expressing P180BCR/ABL from late-appearing Philadelphia-positive acute biphenotypic leukemia.
pubmed:affiliation
Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
pubmed:publicationType
Journal Article, Case Reports