Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development

Jixia Li; Maggie L Kalev-Zylinska

doi:10.3389/fcell.2023.1170622

Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development

Front Cell Dev Biol. 2023 Jun 1:11:1170622. doi: 10.3389/fcell.2023.1170622. eCollection 2023.

Authors

Jixia Li^{1

2}, Maggie L Kalev-Zylinska^{1

3}

Affiliations

¹ Blood and Cancer Biology Laboratory, Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
² Department of Laboratory Medicine, School of Medicine, Foshan University, Foshan, China.
³ Haematology Laboratory, Department of Pathology and Laboratory Medicine, Auckland City Hospital, Auckland, New Zealand.

Abstract

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) in which leukemic blasts have megakaryocytic features. AMKL makes up 4%-15% of newly diagnosed pediatric AML, typically affecting young children (less than 2 years old). AMKL associated with Down syndrome (DS) shows GATA1 mutations and has a favorable prognosis. In contrast, AMKL in children without DS is often associated with recurrent and mutually exclusive chimeric fusion genes and has an unfavorable prognosis. This review mainly summarizes the unique features of pediatric non-DS AMKL and highlights the development of novel therapies for high-risk patients. Due to the rarity of pediatric AMKL, large-scale multi-center studies are needed to progress molecular characterization of this disease. Better disease models are also required to test leukemogenic mechanisms and emerging therapies.

Keywords: acute megakaryoblastic leukemia (AMKL); acute myeloid leukemia; chimeric fusions; cytogenetics; genomics; non-Down syndrome AMKL; therapeutic targets; transcriptomics.

Publication types

Review

Grants and funding

Auckland Medical Research Foundation (funder reference 1119009) and Leukaemia and Lymphoma Research Fund funded from donations by Anne Norman and Victoria Nicholls (UoA grant number 3715253).