Linked Life Data

8124237

Source:http://linkedlifedata.com/resource/pubmed/id/8124237

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1994-4-13
pubmed:abstractText
CML is an excellent target for development of selective treatment because of its highly consistent genetic abnormality t(9;22) and unique fusion gene product, p210bcr/abl, although it is not yet clear what form of specific therapy might be effective. Several components of p210bcr/abl are thought to be essential for its transforming activity: These include the constitutive tyrosine kinase activity of abl and the ability of the first exon for bcr both to specifically bind to abl's SH2 binding domain and possibly also to function as a novel type of serine kinase. Relatively little is yet known about what specific abnormalities in the regulatory pathways are caused by the altered tyrosine kinase activity of p210bcr/abl and other bcr/abl oncoproteins, but whatever its precise mode of action proves to be, p210bcr/abl presumably somehow changes the normal pattern of phosphorylation of key regulatory proteins in the signaling pathways so that the genes which normally direct the orderly sequence of proliferation and maturation of the myeloid progenitors are not properly regulated. The end results of this 'disregulation' are that there is asynchronous or discordant maturation; relative to comparable normal progenitors, a higher proportion of CML progenitors exhibit earlier cytoplasmic and delayed nuclear maturation. The leukemic progenitors do not proliferate more rapidly than comparable normal progenitors or have increased ultimate proliferative potential, but they go through one or more additional divisions during passage through the later maturation compartments and also live longer, resulting in overexpansion of the leukemic population. It is important to recognize the close linkage between maturation and proliferation in designing experiments to correlate the molecular and biological abnormalities and in seeking novel therapies to selectively affect the leukemic progenitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1042-8194
pubmed:author
pubmed:issnType
Print
pubmed:volume
11 Suppl 2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-100
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Integration of molecular and biological abnormalities in quest for selective treatment of chronic myelogenous leukemia (CML).
pubmed:affiliation
Sloan-Kettering Institute for Cancer Research Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't