Deletion of gene for multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16: prognostic implications

Autor:	B.J Kuss, H.J Eyre, S.A Lane, J.K Nancarrow, S.A Whitmore, D.F Callen, R.G Deeley, S.P.C Cole, C.L Willman, K.L Kopecky, Kj Kopecky, S.R Wolman
Rok vydání:	1994
Předmět:	Adult Male Adolescent Drug Resistance Polymerase Chain Reaction Gene dosage Chromosome 16 stomatognathic system hemic and lymphatic diseases medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Gene In Situ Hybridization Fluorescence Retrospective Studies P-glycoprotein Chromosomal inversion Membrane Glycoproteins biology Remission Induction Breakpoint Karyotype General Medicine Middle Aged Prognosis medicine.disease Molecular biology Neoplasm Proteins Leukemia Myeloid Acute Karyotyping Chromosome Inversion Acute myelomonocytic leukemia biology.protein Female Chromosome Deletion Carrier Proteins DNA Probes Chromosomes Human Pair 16
Zdroj:	The Lancet. 343:1531-1534
ISSN:	0140-6736
DOI:	10.1016/s0140-6736(94)92938-6
Popis:	Acute myeloid leukaemia (AML) associated with an inversion in chromosome 16 has a relatively favourable prognosis. The AML subclass most commonly associated with this chromosomal abnormality is acute myelomonocytic leukaemia with abnormal eosinophils. In some AML patients with inversion 16 the chromosomal lesion results in deletion of MRP, the gene for multidrug resistance associated protein. This gene is proximal to the primary breakpoint and loss of its function may play a key role in determining the favourable outcome in inversion 16 AML. We have demonstrated deletion of MRP by in situ hybridisation, by gene dosage studies and by studying loss of heterogeneity of a flanking microsatellite marker. Among 13 AML patients with inversion 16 MRP deletion was detected in 5 while 7 had no deletion. Deletion of MRP gene was associated with longer time from diagnosis until death or relapse from complete remission (p=0·007). These findings provide important insight into the biology of inversion 16 leukaemia and suggest that MRP deletion, as detected by molecular analysis, may have a key role in determining outcome in patients with inversion 16 AML.
Databáze:	OpenAIRE
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