Molecular Mechanisms of the Genetic Predisposition to Acute Megakaryoblastic Leukemia in Infants With Down Syndrome

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Mar 29

PMID 33777792

Citations 17

Authors

Juliane Grimm

Dirk Heckl

Jan-Henning Klusmann

Affiliations

Soon will be listed here.

Abstract

Individuals with Down syndrome are genetically predisposed to developing acute megakaryoblastic leukemia. This myeloid leukemia associated with Down syndrome (ML-DS) demonstrates a model of step-wise leukemogenesis with perturbed hematopoiesis already presenting , facilitating the acquisition of additional driver mutations such as truncating variants, which are pathognomonic to the disease. Consequently, the affected individuals suffer from a transient abnormal myelopoiesis (TAM)-a pre-leukemic state preceding the progression to ML-DS. In our review, we focus on the molecular mechanisms of the different steps of clonal evolution in Down syndrome leukemogenesis, and aim to provide a comprehensive view on the complex interplay between gene dosage imbalances, mutations and somatic mutations affecting JAK-STAT signaling, the cohesin complex and epigenetic regulators.

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