Is the Prenatal Origin of Acute Myeloid Leukaemia Common?

Overview

While there is enough convincing evidence in childhood acute lymphoblastic leukaemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukaemia (AML) are less comprehensive. This study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML patients for the presence of their respective leukaemic markers. Guthrie cards of 13 AML patients (1–14 years) were analysed using 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) as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed to detect the pre-leukaemic clone in Guthrie card provided 1–3 positive cells were present in the neonatal blood spot. Patient-specific molecular markers were not found in any patient with AML. In authors’ previous studies an identical approach was used for patients with ALL and 25% Guthrie cards were found to be positive. The data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukaemic cells is significantly lower at birth in AML compared to ALL cases.

Key words:
prenatal origin, acute myeloid leukaemia, clonal marker