title: Prenatal origin of childhood AML occurs less frequently than in childhood ALL.
abstract: BACKGROUND
  While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers.
  
  
  METHODS
  We analysed Guthrie cards of 12 ALL patients aged 2-6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1-14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1-3 positive cells were present in the neonatal blood spot.
  
  
  RESULTS
  In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML.
  
  
  CONCLUSIONS
  In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases.
authors.affiliation: CLIP-Childhood Leukaemia Investigation Prague, Czech Republic. tana.burjanivova@lfmotol.cuni.cz
authors.forename: Tatiana
authors.initials: T
authors.lastname: Burjanivova
authors.forename: Jozef
authors.initials: J
authors.lastname: Madzo
authors.forename: Katerina
authors.initials: K
authors.lastname: Muzikova
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Bjoern
authors.initials: B
authors.lastname: Schneider
authors.forename: Felix
authors.initials: F
authors.lastname: Votava
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.forename: Jan
authors.initials: J
authors.lastname: Zuna
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001854:Bone Marrow Cells / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000737:chemistry; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000097:blood / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D020440:Gene Duplication; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000097:blood / Q000196:embryology* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000097:blood / Q000235:genetics; D015997:Neonatal Screening; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000097:blood* / Q000235:genetics; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000196:embryology* / Q000453:epidemiology / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3 / Q000097:blood / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D051941:fms-Like Tyrosine Kinase 3; C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; C470550:MLL-AF10 fusion protein, human; C447400:MLL-AF6 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C497970:FLT3 protein, human