Increased levels of a chromosome 21-encoded tumour invasion and metastasis factor (TIAM1) mRNA in bone marrow of Down syndrome children during the acute phase of AML(M7).
Children with Down syndrome (DS) have a 10-20-fold increased risk of acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), compared to non-DS children. The myeloid leukemia that accounts for nearly 50% of DS leukemias is usually the otherwise uncommon megakaryoblastic type (AML-M7). Though an etiological role of trisomy 21 in leukemogenesis has been suggested, the expression of genes on chromosome 21 in relation to trisomy, DS, and specific DS phenotypes such as leukemia is poorly understood. We used a heterologous-mimic competitive RT-PCR technique to measure the mRNA levels of a chromosome 21 tumour invasion and metastasis factor (TIAM1) directly in bone marrow samples of DS leukemic patients. In the limited number of cases analysed so far, we found TIAM1 mRNA levels in the DS AML-M7 samples of bone marrow taken in the acute phase of the disease (presentation or relapse, n=8) to be highly significantly raised, nearly threefold, compared to that measured in the remission samples or normal individuals (normals + remissions, n=10).
Centre for Applied Molecular Biology, School of Pharmacy, University of London, United Kingdom.
J H
JH
Ives
F
F
Dagna-Bricarelli
G
G
Basso
S E
SE
Antonarakis
R
R
Jee
F
F
Cotter
D
D
Nizetić
D000208:Acute Disease; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004314:Down Syndrome / Q000150:complications / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D007947:Leukemia, Megakaryoblastic, Acute / Q000150:complications / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012074:Remission Induction; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D014314:Trisomy
D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D012333:RNA, Messenger; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human