Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemia.
BACKGROUND
Monitoring of minimal residual disease (MRD) has become a strong diagnostic tool in acute lymphoblastic leukemia. It is used for risk-adapted therapy and for the recognition of pending relapses. In acute myeloid leukemia (AML), there is still a need for more suitable MRD markers.


METHODS
A stepwise approach which combined genome-wide expression profiling, TaqMan low density arrays, and a TaqMan real-time PCR-based screening was used to identify new markers for the monitoring of MRD in AML. Leukemic cells from 52 children with AML and 145 follow-up samples from 25 patients were analyzed.


RESULTS
Seven genes were identified which are vastly overexpressed in many patients with AML compared with healthy bone marrow: CCL23, GAGED2, MSLN, SPAG6, and ST18 as well as the previously described markers WT1 and PRAME. The expression of all genes decreased to normal levels in patients who achieved a continuous complete remission. Elevated levels of at least one gene were found prior to relapse in 7 out of 10 patients who relapsed.


CONCLUSIONS
This set of genes should allow a sensitive and specific monitoring of MRD in AML. Notably, some of these markers could also serve as therapeutic targets or might be involved in leukemogenesis. MSLN is already used as a target for immunotherapy in clinical trials in other malignancies.
Steinbach
Daniel
D
University Children's Hospital Jena, Jena, Germany.
Schramm
Alexander
A
Eggert
Angelika
A
Onda
Masanori
M
Dawczynski
Kristin
K
Rump
Andreas
A
Pastan
Ira
I
Wittig
Susann
S
Pfaffendorf
Nadine
N
Voigt
Astrid
A
Zintl
Felix
F
Gruhn
Bernd
B
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D019742:Chemokines, CC / Q000097:blood / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics; D000090204:Mesothelin; D008868:Microtubule Proteins / Q000097:blood / Q000235:genetics; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000097:blood / Q000235:genetics
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C105504:CCL23 protein, human; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D008562:Membrane Glycoproteins; D008868:Microtubule Proteins; C404944:PRAME protein, human; D012097:Repressor Proteins; C400106:SPAG6 protein, human; C497230:ST18 protein, human; D025721:WT1 Proteins; C413656:XAGE1A protein, human; D000090204:Mesothelin