Down syndrome-associated leukaemias: current evidence and challenges

Nicola R. Mason; Hilary Cahill; Yonatan Diamond; Karen McCleary; Rishi S. Kotecha; Glenn M. Marshall; Marion K. Mateos

doi:10.1177/20406207241257901

Down syndrome-associated leukaemias: current evidence and challenges

Nicola R. Mason, Hilary Cahill, Yonatan Diamond, Karen McCleary, Rishi S. Kotecha, Glenn M. Marshall, Marion K. Mateos

Paediatrics

Research output: Contribution to journal › Review article › peer-review

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Abstract

Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS. GATA-binding protein 1 (GATA1) somatic mutations are implicated in the development of transient abnormal myelopoiesis and the progression to myeloid leukaemia of DS (ML-DS) and provide a model of the multi-step process of leukaemogenesis in DS. This review summarises key genetic drivers for the development of leukaemia in patients with DS, the biology and treatment of ML-DS and DS-associated acute lymphoblastic leukaemia, late effects of treatments for DS-leukaemias and the focus for future targeted therapy.

Original language	English
Number of pages	26
Journal	Therapeutic Advances in Hematology
Volume	15
DOIs	https://doi.org/10.1177/20406207241257901
Publication status	E-pub ahead of print - 23 Jul 2024

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title = "Down syndrome-associated leukaemias: current evidence and challenges",

abstract = "Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS. GATA-binding protein 1 (GATA1) somatic mutations are implicated in the development of transient abnormal myelopoiesis and the progression to myeloid leukaemia of DS (ML-DS) and provide a model of the multi-step process of leukaemogenesis in DS. This review summarises key genetic drivers for the development of leukaemia in patients with DS, the biology and treatment of ML-DS and DS-associated acute lymphoblastic leukaemia, late effects of treatments for DS-leukaemias and the focus for future targeted therapy.",

keywords = "acute leukaemia, children, Down syndrome, GATA1, leukaemogenesis, myeloid leukaemia of Down syndrome, transient abnormal myelopoiesis",

author = "Mason, {Nicola R.} and Hilary Cahill and Yonatan Diamond and Karen McCleary and Kotecha, {Rishi S.} and Marshall, {Glenn M.} and Mateos, {Marion K.}",

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T1 - Down syndrome-associated leukaemias

T2 - current evidence and challenges

AU - Mason, Nicola R.

AU - Cahill, Hilary

AU - Diamond, Yonatan

AU - McCleary, Karen

AU - Kotecha, Rishi S.

AU - Marshall, Glenn M.

AU - Mateos, Marion K.

N1 - Publisher Copyright: © The Author(s), 2024.

PY - 2024/7/23

Y1 - 2024/7/23

N2 - Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS. GATA-binding protein 1 (GATA1) somatic mutations are implicated in the development of transient abnormal myelopoiesis and the progression to myeloid leukaemia of DS (ML-DS) and provide a model of the multi-step process of leukaemogenesis in DS. This review summarises key genetic drivers for the development of leukaemia in patients with DS, the biology and treatment of ML-DS and DS-associated acute lymphoblastic leukaemia, late effects of treatments for DS-leukaemias and the focus for future targeted therapy.

AB - Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS. GATA-binding protein 1 (GATA1) somatic mutations are implicated in the development of transient abnormal myelopoiesis and the progression to myeloid leukaemia of DS (ML-DS) and provide a model of the multi-step process of leukaemogenesis in DS. This review summarises key genetic drivers for the development of leukaemia in patients with DS, the biology and treatment of ML-DS and DS-associated acute lymphoblastic leukaemia, late effects of treatments for DS-leukaemias and the focus for future targeted therapy.

KW - acute leukaemia

KW - children

KW - Down syndrome

KW - GATA1

KW - leukaemogenesis

KW - myeloid leukaemia of Down syndrome

KW - transient abnormal myelopoiesis

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U2 - 10.1177/20406207241257901

DO - 10.1177/20406207241257901

M3 - Review article

C2 - 39050114

AN - SCOPUS:85199382377

SN - 2040-6207

VL - 15

JO - Therapeutic Advances in Hematology

JF - Therapeutic Advances in Hematology

ER -

Down syndrome-associated leukaemias: current evidence and challenges

Abstract

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