Transient myeloproliferative disorder (TMD), also known as transient abnormal myelopoiesis (TAM), is a myeloproliferative condition that occurs in the perinatal period in up to 10% of patients who have Down syndrome. Hepatomegaly, splenomegaly, pericardial/pleural effusions, and skin rash are the clinical features of TAM most frequently seen in neonates with GATA1 mutation. Most neonates undergo spontaneous resolution.

TAM is characterized by increased circulating blasts. The blast cells harbor N-terminal truncating mutations in the transcription factor gene GATA1. Neonates with Down syndrome who develop TAM have circulating blasts greater than ten percent, causing them to develop typical clinical features that may require close monitoring.

To understand the events of TAM and Myeloid leukemia of Down syndrome (ML-DS) at a cellular and molecular level, a three-step model is proposed with hits involving a progenitor hematopoetic stem cell. These hits include (1) an acquired GATA mutation, (2) Trisomy 21, and (3) at least one additional oncogenic mutation [1]. Silent TAM occurs in the neonates who have a GATA1 mutation but no clinical features.

The immunophenotype of TAM is variable: the characteristic pattern of co-expression of stem cell markers (CD34 and CD117), myeloid markers (CD33/CD13), platelet glycoproteins (CD36, CD42, CD61) together with CD56 and CD7 .

References:

[1] Bhatnagar N, Nizery L, Tunstall O, Vyas P, Roberts I. Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update. Curr Hematol Malig Rep. 2016;11(5):333-341.