PMID- 9680348
OWN - NLM
STAT- MEDLINE
DCOM- 19980827
LR  - 20220331
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 92
IP  - 3
DP  - 1998 Aug 1
TI  - Presence of a p53 gene deletion in patients with multiple myeloma predicts for 
      short survival after conventional-dose chemotherapy.
PG  - 802-9
AB  - In multiple myeloma (MM), previous studies showed that mutations of the p53 gene 
      are rare events in patients with newly diagnosed disease, but it is not known 
      whether deletions of p53 are of any significance in MM. To address this question, 
      we used interphase fluorescence in situ hybridization (FISH) with a DNA probe 
      specific for the p53 locus at 17p13 and investigated bone marrow plasma cells 
      from 72 patients with MM (59 patients = 81.9% before therapy). By FISH, deletions 
      of p53, which were found to be predominantly monoallelic, were detected in 32.8% 
      and 54.5% of patients with newly diagnosed and relapsed MM, respectively. 
      Karyotypes from six of the patients with a p53 deletion by FISH showed a 
      structural abnormality of 17p in only one of them. Additional FISH studies 
      including a distal-17p probe (specific for the D17S34 locus) provided evidence 
      for an interstitial deletion on 17p resulting in loss of p53 hybridization 
      signals in myeloma cells. Among all 59 patients with newly diagnosed MM, presence 
      of a p53 deletion was associated with stage III (P = .054), but not with other 
      laboratory and clinical parameters. Patients with a p53 deletion had 
      significantly shorter survival time compared with those without a deletion, both 
      from the time of diagnosis (median 13.9 v 38.7 months; P < .0001) and from the 
      time of initiation of induction treatment consisting of conventional dose 
      chemotherapy (median 15.9 months v median not reached at 38 months; P < .0002). 
      On stepwise multivariate regression analysis, presence of a p53 deletion was the 
      most significant independent parameter predicting for shortened survival (P = 
      .002). We conclude that a p53 gene deletion, which can be identified by 
      interphase FISH in almost a third of patients with newly diagnosed MM, is a novel 
      prognostic factor predicting for short survival of MM patients treated with 
      conventional-dose chemotherapy.
CI  - Copyright 1998 by The American Society of Hematology.
FAU - Drach, J
AU  - Drach J
AD  - First Department of Internal Medicine, the Division of Clinical Oncology, 
      University of Vienna, Vienna, Austria. johannes.drach@akh-wien.ac.at
FAU - Ackermann, J
AU  - Ackermann J
FAU - Fritz, E
AU  - Fritz E
FAU - Kromer, E
AU  - Kromer E
FAU - Schuster, R
AU  - Schuster R
FAU - Gisslinger, H
AU  - Gisslinger H
FAU - DeSantis, M
AU  - DeSantis M
FAU - Zojer, N
AU  - Zojer N
FAU - Fiegl, M
AU  - Fiegl M
FAU - Roka, S
AU  - Roka S
FAU - Schuster, J
AU  - Schuster J
FAU - Heinz, R
AU  - Heinz R
FAU - Ludwig, H
AU  - Ludwig H
FAU - Huber, H
AU  - Huber H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 5J49Q6B70F (Vincristine)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - Q41OR9510P (Melphalan)
RN  - U68WG3173Y (Carmustine)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Bone Marrow/chemistry/pathology
MH  - Carmustine/administration & dosage
MH  - Chromosomes, Human, Pair 17/*genetics/ultrastructure
MH  - Cyclophosphamide/administration & dosage
MH  - Dexamethasone/administration & dosage
MH  - Female
MH  - *Gene Deletion
MH  - *Genes, p53
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase
MH  - Karyotyping
MH  - Life Tables
MH  - Male
MH  - Melphalan/administration & dosage
MH  - Middle Aged
MH  - Multiple Myeloma/drug therapy/*genetics/mortality
MH  - Prednisone/administration & dosage
MH  - Prognosis
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Vincristine/administration & dosage
EDAT- 1998/07/29 00:00
MHDA- 1998/07/29 00:01
CRDT- 1998/07/29 00:00
PHST- 1998/07/29 00:00 [pubmed]
PHST- 1998/07/29 00:01 [medline]
PHST- 1998/07/29 00:00 [entrez]
AID - S0006-4971(20)53697-5 [pii]
PST - ppublish
SO  - Blood. 1998 Aug 1;92(3):802-9.