PMID- 12531801
OWN - NLM
STAT- MEDLINE
DCOM- 20030718
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 10
DP  - 2003 May 15
TI  - Continuous absence of metaphase-defined cytogenetic abnormalities, especially of 
      chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma 
      treated with Total Therapy I: interpretation in the context of global gene 
      expression.
PG  - 3849-56
AB  - Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), 
      confer a grave prognosis in multiple myeloma even with tandem 
      autotransplantations as applied in Total Therapy I, which enrolled 231 patients 
      between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic 
      implications of all individual CAs, detected prior to treatment and at relapse, 
      were investigated. Among all CAs and standard prognostic factors examined prior 
      to therapy, only hypodiploidy and CA 13 (hypo-13 CA), alone or in combination, 
      were associated with shortest event-free survival and overall survival (OS). The 
      shortest postrelapse OS was observed with hypo-13 CA, which was newly detected in 
      18 of all 28 patients presenting with this abnormality at relapse. Superior 
      prognosis was associated with the absence of any CA at both diagnosis and relapse 
      (10-year OS, 40%). The lack of independent prognostic implications of other CAs 
      points to a uniquely aggressive behavior of hypo-13 CA (present in 16% of 
      patients at diagnosis). With the use of microarray data in 146 patients enrolled 
      in Total Therapy II, overexpression of cell cycle genes distinguished CA from no 
      CA, especially in cases of del(13) detected by interphase fluorescence in situ 
      hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other 
      genes mapping to chromosome 13, as well as activation of IGF1R, appears to have 
      an amplifying effect on cell cycle gene expression, thus providing a molecular 
      explanation for the dire outcome of patients with CA 13 compared with those with 
      other CAs.
FAU - Shaughnessy, John
AU  - Shaughnessy J
AD  - Myeloma Institute for Research and Therapy, University of Arkansas for Medical 
      Sciences, Little Rock, AR 72205, USA.
FAU - Jacobson, Joth
AU  - Jacobson J
FAU - Sawyer, Jeff
AU  - Sawyer J
FAU - McCoy, Jason
AU  - McCoy J
FAU - Fassas, Athanasios
AU  - Fassas A
FAU - Zhan, Fenghuang
AU  - Zhan F
FAU - Bumm, Klaus
AU  - Bumm K
FAU - Epstein, Joshua
AU  - Epstein J
FAU - Anaissie, Elias
AU  - Anaissie E
FAU - Jagannath, Sundar
AU  - Jagannath S
FAU - Vesole, David
AU  - Vesole D
FAU - Siegel, David
AU  - Siegel D
FAU - Desikan, Raman
AU  - Desikan R
FAU - Munshi, Nikhil
AU  - Munshi N
FAU - Badros, Ashraf
AU  - Badros A
FAU - Tian, Erming
AU  - Tian E
FAU - Zangari, Maurizio
AU  - Zangari M
FAU - Tricot, Guido
AU  - Tricot G
FAU - Crowley, John
AU  - Crowley J
FAU - Barlogie, Bart
AU  - Barlogie B
LA  - eng
GR  - CA55819/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030116
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - *Chromosome Aberrations
MH  - *Chromosomes, Human, Pair 13
MH  - Diploidy
MH  - Follow-Up Studies
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Metaphase/genetics
MH  - Multiple Myeloma/*drug therapy/*genetics
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Time Factors
EDAT- 2003/01/18 04:00
MHDA- 2003/07/19 05:00
CRDT- 2003/01/18 04:00
PHST- 2003/01/18 04:00 [pubmed]
PHST- 2003/07/19 05:00 [medline]
PHST- 2003/01/18 04:00 [entrez]
AID - S0006-4971(20)44428-3 [pii]
AID - 10.1182/blood-2002-09-2873 [doi]
PST - ppublish
SO  - Blood. 2003 May 15;101(10):3849-56. doi: 10.1182/blood-2002-09-2873. Epub 2003 
      Jan 16.