Prenatal origin of childhood AML occurs less frequently than in childhood ALL

Tatiana Burjanivova,Katerina Muzikova,Claus Meyer,Jan Stary,Felix Votava,Jan Trka,Bjoern Schneider,Jozef Madzo,Rolf Marschalek,Jan Zuna

doi:10.1186/1471-2407-6-100

Tatiana Burjanivova, Katerina Muzikova + Show 8 more

Open Access

https://doi.org/10.1186/1471-2407-6-100

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Journal: BMC Cancer	Publication Date: Apr 21, 2006
Citations: 61	License type: cc-by

Affiliation: Goethe University Frankfurt, Charles University

Abstract

BackgroundWhile 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.MethodsWe 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.ResultsIn 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.ConclusionIn 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.

Highlights

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
Desired sensitivity was > = 10-4 (i.e. 1 cell from diagnostic sample among 10 000 other cells). We reached this sensitivity in all systems and in all experiments except for 2 AML patients (AML13 and AML8) who presented with a low blast percentage (5.2 and 30%, respectively) at diagnosis
It is more demanding to perform a large Guthrie card study on AML patients compared to ALL – the diagnosis is about five times less frequent and there is no universal marker for the genetic screening in AML cases

Summary

Introduction

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. Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer while acute myeloid leukemia (AML) occurs approximately 5 times less frequently in children. There is evidence that some childhood acute leukemias originate in utero. Gale et al backtracked MLL/AF4 fusion gene, a leukemo-specific clonal marker, to neonatal dried blood spots on filter-paper (Guthrie cards) of 3 children who developed ALL at the ages of 5 months to 2 years [2]. Guthrie cards positive for the TEL/AML1 (ETV6/RUNX1) were found in more than 10 ALL patients with this fusion gene [3,4,5,6]

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