TY - JOUR
T1 - Molecular insights into Down syndrome-associated leukemia
AU - Vyas, Paresh
AU - Crispino, John D.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2007/2
Y1 - 2007/2
N2 - PURPOSE OF REVIEW: Four years ago it was discovered that nearly all cases of transient myeloproliferative disorder and acute megakaryocytic leukemia in children with Down syndrome acquire mutations in the hematopoietic transcription factor gene GATA1. Studies within the past year, described within this review, have provided tremendous insights into the role of GATA1 mutations in these malignancies. RECENT FINDINGS: In the past year, our understanding of the molecular and cellular consequences of GATA1 mutations has been greatly enhanced. Most importantly, we have learned that these mutations, which result in the exclusive production of the short GATA1 isoform named GATA1s, have a distinct effect on fetal liver progenitors. In addition, multiple studies have shown that GATA1s can substitute for GATA1 in many aspects of megakaryocytic maturation. Finally, an important clinical study has revealed that GATA1 mutations alone are insufficient for leukemia. SUMMARY: Leukemia in children with Down syndrome requires at least three cooperating events - trisomy 21, a GATA1 mutation, and a third, as yet undefined, genetic alteration. Recent studies have provided tremendous insights into the GATA1 side of the story. Future experiments with human patient samples and mouse models will likely increase our awareness of the role of trisomy 21 in transient myeloproliferative disorder and acute megakaryocytic leukemia.
AB - PURPOSE OF REVIEW: Four years ago it was discovered that nearly all cases of transient myeloproliferative disorder and acute megakaryocytic leukemia in children with Down syndrome acquire mutations in the hematopoietic transcription factor gene GATA1. Studies within the past year, described within this review, have provided tremendous insights into the role of GATA1 mutations in these malignancies. RECENT FINDINGS: In the past year, our understanding of the molecular and cellular consequences of GATA1 mutations has been greatly enhanced. Most importantly, we have learned that these mutations, which result in the exclusive production of the short GATA1 isoform named GATA1s, have a distinct effect on fetal liver progenitors. In addition, multiple studies have shown that GATA1s can substitute for GATA1 in many aspects of megakaryocytic maturation. Finally, an important clinical study has revealed that GATA1 mutations alone are insufficient for leukemia. SUMMARY: Leukemia in children with Down syndrome requires at least three cooperating events - trisomy 21, a GATA1 mutation, and a third, as yet undefined, genetic alteration. Recent studies have provided tremendous insights into the GATA1 side of the story. Future experiments with human patient samples and mouse models will likely increase our awareness of the role of trisomy 21 in transient myeloproliferative disorder and acute megakaryocytic leukemia.
KW - Down syndrome
KW - GATA1
KW - Megakaryocytic leukemia
KW - Trisomy 21
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U2 - 10.1097/MOP.0b013e328013e7b2
DO - 10.1097/MOP.0b013e328013e7b2
M3 - Review article
C2 - 17224656
AN - SCOPUS:33846268788
VL - 19
SP - 9
EP - 14
JO - Current Opinion in Pediatrics
JF - Current Opinion in Pediatrics
SN - 1040-8703
IS - 1
ER -