Transient myeloproliferative disorder with partial trisomy 21

Area of Science:

• Genetics
• Hematology
• Oncology

Background:

• Myeloid malignancy with Down syndrome (ML-DS) is a complex hematologic disorder.
• Leukemogenesis in ML-DS is thought to involve GATA1 mutations and Trisomy 21.
• The specific genes on chromosome 21 contributing to ML-DS remain largely unidentified.

Purpose of the Study:

• To investigate the genetic basis of ML-DS in an infant with transient myeloproliferative disorder (TMD) and partial Trisomy 21.
• To identify candidate genes on chromosome 21 involved in ML-DS pathogenesis.

Main Methods:

• Case report of a female infant with TMD and partial Trisomy 21.
• SNP array analysis to determine the extent of chromosome 21 amplification.
• Comparative analysis with previously reported TMD cases.

Main Results:

• The infant presented with transient myeloproliferative disorder (TMD) and partial Trisomy 21.
• SNP array revealed a 10 Mb amplification on 21q22.12-21q22.3, encompassing DYRK1A, ERG, and ETS genes.
• RUNX1 gene was not included in the amplified region.

Conclusions:

• DYRK1A, ERG, and ETS are identified as likely candidate genes involved in ML-DS.
• These genes may collaborate with GATA1 mutations in the development of myeloid malignancy in Down syndrome.