Enhanced insulin-receptor tyrosine kinase activity associated with chromosomal translocation (1;19) in a pre-B-cell leukemia line.
The gene for the insulin receptor has been assigned to chromosome 19 near the breakpoint of the translocation t(1;19) which occurs in 25% of pre-B-cell leukemias. Insulin receptors in a pre-B-cell leukemia cell line (ACV) with t(1;19) were found to have 2-fold higher affinity for insulin, 5-fold higher basal and insulin-stimulated beta sub-unit autophosphorylation, and 2-fold higher basal and 4-fold higher insulin-stimulated beta sub-unit kinase activity on the synthetic peptide poly(Glu,Tyr), compared to receptors in a B-cell line (ADD) with normal karyotype from the same patient. ACV cells had a novel 13-kb receptor mRNA species and expressed a DNA polymorphism localized to the tyrosine kinase domain of the receptor gene. These findings suggest that t(1;19) in the ACV cell may result in rearrangement of the insulin receptor gene and translation of a receptor with enhanced tyrosine kinase activity.
Newman
J D
JD
Burnet Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Harrison
L C
LC
Eckardt
G S
GS
Jack
I
I
D015152:Blotting, Northern; D015139:Blotting, Southern; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011972:Receptor, Insulin / Q000378:metabolism; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007328:Insulin; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin