Abstract
Abstract 4680
One of the most common human chromosomal abnormalities, Down syndrome, is caused by trisomy 21. Transient myeloproloferative disorders (TMD) occur in 10-20 % of newborns with Down syndrome. About 30 % of those TMD patients develop Acute Megakaryoblastic Leukemia (AMKL) within 4 years. Therefore both disorders have their origin in the fetus. There is emerging evidence that the protein product of GATA1 mutations, GATA1s, directly contributes to leukemogenesis. Although an in utero origin of GATA1 mutations and consecutively TMD is established it was never analyzed if GATA1 mutations could be detected in maternal PBL collected before and after the delivery of a child with Down syndrome and TMD. We therefore initiated a study to detect mutant GATA1 in three pairs of mother and child (A, B, C).
After the identification of the specific GATA1 mutations of the newborn with TMD, PBL samples of the mothers drawn 4 days after delivery (mother A), 7 days after delivery (mother B) and 4 week before as well as just before sectio cesarea ( mother C) were analyzed.
All 3 patients had duplications in exon 2. Patient A had a duplication of 191 bp including the start codon,, patient B showed a duplication of 2 bp, and patient C had a duplication of 13 bp, respectively.
The three mothers harbored the TMD specific GATA1 mutations in PBL analyzed around the birth of their children.
The GATA1s signal in mother A and B had disappeared 1 month after birth. No analysis at this time point was done in mother C,whereas she was positive for the specific GATA1 mutation one month before delivery. At that time TMD was suggested by ultrasound which revealed clinical signs of hydrops in the fetus.
In mother B and C the particular GATA1 mutations could also be detected in their plasma, in the plasma sample of mother C even 4 weeks before delivery (not done in mother A).
In our study we could show for the first time that GATA1 mutations of leukemic cells could be detected in PBL of the mothers around birth. Cell free GATA1 DNA was also detectable. The prenatal finding of TMD specific mutations in the mothers' blood suggests that feto-maternal transfer of leukemic cells and DNA may already occur up to 4 weeks before delivery.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
