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. CONCLUSION: 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.

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma blood   embryology   epidemiology   genetics   MeSH
• Clone Cells chemistry   MeSH
• Bone Marrow Cells chemistry   MeSH
• Child MeSH
• DNA, Neoplasm blood   MeSH
• Gene Duplication MeSH
• Fetal Blood chemistry   MeSH
• Oncogene Proteins, Fusion blood   genetics   MeSH
• Gene Rearrangement, B-Lymphocyte * MeSH
• Gene Rearrangement, T-Lymphocyte * MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Leukemia, Myeloid blood   embryology   epidemiology   genetics   MeSH
• Biomarkers, Tumor blood   MeSH
• Neoplasm Proteins blood   genetics   MeSH
• Infant, Newborn MeSH
• Neonatal Screening MeSH
• Polymerase Chain Reaction MeSH
• Child, Preschool MeSH
• Core Binding Factor Alpha 2 Subunit blood   genetics   MeSH
• RUNX1 Translocation Partner 1 Protein MeSH
• Myeloid-Lymphoid Leukemia Protein blood   genetics   MeSH
• Tandem Repeat Sequences MeSH
• fms-Like Tyrosine Kinase 3 blood   genetics   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• AML1-ETO fusion protein, human MeSH Browser
• CBFbeta-MYH11 fusion protein MeSH Browser
• DNA, Neoplasm MeSH
• FLT3 protein, human MeSH Browser
• Oncogene Proteins, Fusion MeSH
• MLL-AF10 fusion protein, human MeSH Browser
• MLL-AF6 fusion protein, human MeSH Browser
• Biomarkers, Tumor MeSH
• Neoplasm Proteins MeSH
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein MeSH Browser
• Core Binding Factor Alpha 2 Subunit MeSH
• RUNX1 Translocation Partner 1 Protein MeSH
• Myeloid-Lymphoid Leukemia Protein MeSH
• TEL-AML1 fusion protein MeSH Browser
• fms-Like Tyrosine Kinase 3 MeSH