Transient myeloproliferative disorder (TMD), now more commonly known as transient abnormal myelopoiesis (TAM), is a condition closely associated with Down syndrome. Ninety-five percent of Down syndrome cases occur as a result of chromosomal nondisjunction and are rarely due to mosaicism or translocation. TMD is found exclusively in neonates and is most commonly characterized by trisomy 21, somatic GATAI mutation, and the increased presence of megakaryoblasts. TMD often does not manifest clinically, but patients may show hepatomegaly, splenomegaly and other symptoms. While TMD is almost always present with trisomy 21, there are not many other cytogenetic abnormalities associated with TMD, with a few rare cases such as monosomy 7 and trisomy 8. Recentstudies have suggested liver hematopoietic progenitor cells as the candidate for TMD origin. Furthermore, GATAI mutations associated with TMD are found to encode for a stop codon in the N-terminal activation region of gene sequences. It has been shown that those mutations can cause overproliferation of megakaryocytes, which can cooperate with Down syndrome cells, which have trisomy 21, in the progression of TMD into acute megakaryoblastic leukemia (AMKL). Since GATAI mutations are present in all casesof myeloid leukemia of Down Syndrome, monitoring GATAI in patients with trisomy 21 may assist with earlier diagnosis of TMD. Another likely cause of TMD is the amplification of the RUNXI transcription factor gene located on chromosome 21. It has been shown that RUNXI is associated with leukemias of myeloid lineage. While most cases of TMD will spontaneously resolve, some will evolve into acute myeloid leukemia (AML). In this review, we will discuss the cytogenetic, molecular genetics and clinical aspects of TMD.
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