PMID- 19901261
OWN - NLM
STAT- MEDLINE
DCOM- 20100128
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 115
IP  - 2
DP  - 2010 Jan 14
TI  - Strikingly different molecular relapse kinetics in NPM1c, PML-RARA, 
      RUNX1-RUNX1T1, and CBFB-MYH11 acute myeloid leukemias.
PG  - 198-205
LID - 10.1182/blood-2009-04-212530 [doi]
AB  - Early relapse detection in acute myeloid leukemia is possible using standardized 
      real-time quantitative polymerase chain reaction (RQ-PCR) protocols. However, 
      optimal sampling intervals have not been defined and are likely to vary according 
      to the underlying molecular lesion. In 74 patients experiencing hematologic 
      relapse and harboring aberrations amenable to RQ-PCR (mutated NPM1 [designated 
      NPM1c], PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11), we observed strikingly 
      different relapse kinetics. The median doubling time of the CBFB-MYH11 leukemic 
      clone was significantly longer (36 days) than that of clones harboring other 
      markers (RUNX1-RUNX1T1, 14 days; PML-RARA, 12 days; and NPM1c, 11 days; P < 
      .001). Furthermore, we used a mathematical model to determine frequency of 
      relapse detection and median time from detection of minimal residual disease to 
      hematologic relapse as a function of sampling interval length. For example, to 
      obtain a relapse detection fraction of 90% and a median time of 60 days, blood 
      sampling every sixth month should be performed for CBFB-MYH11 leukemias. By 
      contrast, in NPM1c(+)/FLT3-ITD(-), NPM1c(+)/FLT3-ITD(+), RUNX1-RUNX1T1, and 
      PML-RARA leukemias, bone marrow sampling is necessary every sixth, fourth, and 
      fourth and second month, respectively. These data carry important implications 
      for the development of optimal RQ-PCR monitoring schedules suitable for 
      evaluation of minimal residual disease-directed therapies in future clinical 
      trials.
FAU - Ommen, Hans Beier
AU  - Ommen HB
AD  - Laboratory of Immunohematology, Department of Hematology, Aarhus University 
      Hospital, Aarhus, Denmark.
FAU - Schnittger, Susanne
AU  - Schnittger S
FAU - Jovanovic, Jelena V
AU  - Jovanovic JV
FAU - Ommen, Ingrid Beier
AU  - Ommen IB
FAU - Hasle, Henrik
AU  - Hasle H
FAU - Ostergaard, Mette
AU  - Ostergaard M
FAU - Grimwade, David
AU  - Grimwade D
FAU - Hokland, Peter
AU  - Hokland P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091109
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (AML1-ETO fusion protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CBFB protein, human)
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (Core Binding Factor beta Subunit)
RN  - 0 (MYH11 protein, human)
RN  - 0 (NPM1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RUNX1 Translocation Partner 1 Protein)
RN  - 0 (promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein)
RN  - 117896-08-9 (Nucleophosmin)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Biomarkers, Tumor/*biosynthesis/genetics
MH  - Bone Marrow/metabolism
MH  - Core Binding Factor Alpha 2 Subunit/*biosynthesis/genetics
MH  - Core Binding Factor beta Subunit/*biosynthesis/genetics
MH  - Female
MH  - *Gene Expression Regulation, Leukemic
MH  - Humans
MH  - Kinetics
MH  - Leukemia, Myeloid, Acute/genetics/*metabolism/therapy
MH  - Male
MH  - Monitoring, Physiologic/methods
MH  - Myosin Heavy Chains/*biosynthesis/genetics
MH  - Neoplasm, Residual
MH  - Nuclear Proteins/*biosynthesis/genetics
MH  - Nucleophosmin
MH  - Oncogene Proteins, Fusion/*biosynthesis/genetics
MH  - RUNX1 Translocation Partner 1 Protein
MH  - Recurrence
MH  - Retrospective Studies
MH  - Time Factors
EDAT- 2009/11/11 06:00
MHDA- 2010/01/29 06:00
CRDT- 2009/11/11 06:00
PHST- 2009/11/11 06:00 [entrez]
PHST- 2009/11/11 06:00 [pubmed]
PHST- 2010/01/29 06:00 [medline]
AID - S0006-4971(20)49350-4 [pii]
AID - 10.1182/blood-2009-04-212530 [doi]
PST - ppublish
SO  - Blood. 2010 Jan 14;115(2):198-205. doi: 10.1182/blood-2009-04-212530. Epub 2009 
      Nov 9.