Abstract

Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies.

Highlights

  • Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are heterogenous diseases of hematopoietic stem cells and progenitor cells

  • Using the CustomArray platform, we synthesized the arrays with 2228 oligonucleotide probes corresponding to 2016 human genes involved in 334 intracellular signaling pathways (Supplementary dataset S2)

  • It is widely accepted that the cellular physiology, epigenetic regulation and gene expression of normal hematopoietic stem cells change with age, molecular grounds of such age-dependent cancer transformation remain largely unknown [1]

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Summary

Introduction

Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are heterogenous diseases of hematopoietic stem cells and progenitor cells. AML is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells [1]. AML involves high percentages of dedifferentiated and undifferentiated cells, including blasts (myeloblasts, monoblasts and megakaryoblasts) [2]. AML is relatively www.aging‐us.com rare in the childhood, but it is the most common acute leukemia affecting adults, and its incidence increases with age [3]. AML progresses rapidly and is typically fatal within weeks or months if left untreated. AML is cured in 35–40% of people under 60 and in 5–15% of patients over 60 respectively [2]

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