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Analysis of mutations in the GM-CSF receptor alpha coding sequence in patients with acute myeloid leukaemia and haematologically normal individuals by RT-PCR-SSCP.

Abstract：

:Mutations of signal transducing molecules such as Ras have been shown to confer a growth advantage in leukaemic blasts and contribute to the pathogenesis of the disease. Alterations of signal transducing molecules other than Ras may play a role in leukaemogenesis. Knowledge of such mutations could also further our understanding of the normal signalling processes. We have therefore studied the coding sequence of the GM-CSF receptor alpha chain (GM-CSFR alpha) in patients with acute myeloid leukaemia (AML) and non-AML controls using single strand conformation polymorphism (SSCP) analysis. Abnormalities were detected in 4/32 AML patients (13%) and 2/15 non-AML controls (13%). Direct sequencing of PCR products revealed five different base substitutions. Three were conservative, two caused amino acid changes. The base substitution leading to amino acid change alanine to glycine at position 17 was found in both an AML patient and a control. It lies in the signal sequence and does not affect the mature protein. The other base change altering arginine to glutamine at position 164 is unlikely to influence the receptor structure as this structural position in the chain is not well conserved in members of the cytokine receptor family. Both amino acid changes were constitutive alterations as they could be demonstrated in the patients' children. The base changes described in the AML patients thus represent polymorphisms and do not contribute to the pathogenesis of AML.

journal_name

Leukemia

journal_title

Leukemia

authors

Wagner HM,Gale RE,Freeburn RW,Devereux S,Linch DC

subject

Has Abstract

pub_date

1994-09-01 00:00:00

pages

1527-32

issue

9

eissn

0887-6924

issn

1476-5551

journal_volume

8

pub_type

杂志文章

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