Cytogenetics of pediatric acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease accounting for 15–20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. This article focuses on the significance of cytogenetic analysis in pediatric AML supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow‐up and treatment selection in childhood AML. It reviews in detail the types and frequencies of most common chromosomal aberrations, their molecular background, their correlation with French American British (FAB) subtypes and age distribution and their prognostic relevance. It also summarizes some less frequent or rare chromosome aberrations in which the prognostic classification has not been determined yet owning to the small number of patients and the variable treatment modalities used in different study groups. Furthermore, it discusses the association of specific chromosome rearrangements with prenatal exposure to carcinogenic agents or therapeutic agents and highlights the ongoing and future research on pediatric AML in the evolving field of Cytogenetics.

Acute Myeloid Leukemia in Children: Experience from Tertiary Cancer Centre in India

“…However, we have not included patients who were not treated because of their moribund condition or those who refused treatment, the outcomes would be inferior if these patients were also analysed. Cytogenetic profile in our study was similar to western population and was the only factor that predicted survival [4]. The reason why patients with intermediate or poor risk cytogenetics patients had inferior outcomes compared to western data was because majority of these patients could not undergo allogenic stem cell transplantation due to financial constraints [9].…”

“…Diagnosis of AML was confirmed by bone marrow aspiration morphology and flow cytometry. Patients were stratified for risk according to the bone marrow cytogenetic analysis report [4]. Patients with t(8;21) or inv(16) in the leukemic cells were classified as having favourable cytogenetics, patients with normal karyotype, acquired ?21 or t(9;11) were classified as having intermediate cytogenetics and patients with complex cytogenetics (three or more karyotype abnormalities), -5/del 5q, -7/del 7q, ?8, t(8;16), t(11q23), t(16;21), t(9;22), t(1;22), inv(3), t(3;3), t(6;9), t(7;12) or del 9q abnormalities were classified as high risk cytogenetics.…”

Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

“…12 The age-dependent incidence patterns we observed are consistent with the age-specific patterns of recurrent chromosomal and genetic abnormalities that are a hallmark of AL. [13][14][15][16] For example, the Philadelphia chromosome t(9;22) is the most common rearrangement in adult ALL/L, whereas high hyperdiploidy (51-65 chromosomes) and the t(12;21) translocation are the most common cytogenetic abnormalities in childhood ALL/L. In both infant ALL/L and AML, the t(4;11) translocation involving the MLL gene is the most common abnormality.…”

High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine

“…9 Similarly, the numbers of patients with favorable and intermediate cytogenetic aberrations were lower than previously described for unselected patients. 42 The selected group is representative for patients with relapsed AML in terms of TTR rates, because approximately one-half of the relapses (57%) were early relapses and occurred within 1 year from diagnosis. 1 The 2-year OS rate was 36%, which is lower compared with all patients with newly diagnosed pediatric AML treated with similar protocols and in line with previous reports on outcome of children with relapsed AML.…”