Mystery Baby

Researchers take a look at transient abnormal myelopoiesis (TAM) in Down Syndrome patients

Transient abnormal myelopoiesis (TAM) is a unique disorder of newborns associated closely with Down syndrome (5-10%). Clinical and morphological features are indistinguishable from acute myeloid leukemia (AML). Most cases of TAM resolve with spontaneous remission over the first few months of life, but a small percentage may go on to develop AML within the first four years of life.1

Tech Perspective

What is the most likely diagnosis? Acute Leukemia.

What subsequent actions would you take?Gather clinical data and information, pathology involvement.

What definitive test would be needed? Bone marrow, flow cytometry and genetic markers.

Definitive Tests

Flow Cytometry

  • No difference between Acute Megakaryoblastic Leukemia(AML) and Transient Abnormal Mylelopoiesis.2, 3
  • Myelopoiesis(TAM). Flow cytometry CD markers C41 and C61 are the two makers differentiating M7 in AML. This allows clinicians to differentiate it between other Acute Myeloid Leukemias.3

Genetic Tests for Acute Megakaryoblastic Leukemia(AML-M7)

  • Children with Down syndrome have an increased risk of Acute Myeloid Leukemia, particularly megakaryoblastic leukemia.
  • Cases of AML-M7 can have chromosomal abnormalities that have not been described in TAM, one of them is t(1;22).1

Acute Megakaryoblastic Leukemia(AML-M7)

  • Is defined by more than 20% (WHO classifications) or 30% (FAB classifications) of blasts of megakaryocytic lineage in the bone marrow aspirate as determined by morphology and immunoflowcytometry.4


A baby boy was diagnosed with Down syndrome and was sent to children’s hospital to be evaluated after clinical evaluation and findings on his CBC and Coagulation Studies. Clinical symptoms were not available to the technologist. Genetic testing and further follow-up discovered that the infant was diagnosed with Transient Abnormal Myelopoiesis (TAM) by the pathologist.

TAM is characterized by an increase in the number of myeloblasts, and has morphologic and immunophenotypic features characteristic of megakaryoblastic leukemia.1,3

Individuals with Down syndrome (DS) run a risk of developing acute leukemia, which is increased 10-100-fold. Children with Down syndrome are at increased risk for developing acute myeloid leukemia (AML) (approximately 1-2% of children with Down syndrome develop AML, the great majority of which are less than 5 years old) rather than acute lymphoblastic leukemia (ALL), the most common form of leukemia in children. Disorders associated with trisomy 21, transient abnormal myelopoiesis (TAM) and myeloid leukemia can accompany Down syndrome.1,3

TAM is most often reported in newborns with Down syndrome (5-10%). This condition can also be occasionally found in phenotypically normal neonates; some of these neonates are found to be mosaic for trisomy 21. TAM resolves spontaneously in the majority of cases, and the term transient abnormal myelopoiesis is then used. A significant percentage of the cases that do not resolve spontaneously (20-30%) progress to acute megakaryoblastic leukemia within 1-4 years from the time of the diagnosis.1, 3 AML associated with Down syndrome is most often megakaryoblastic. It should be recognized and understood that both myelodysplastic syndrome (MDS) and AML that result in a patient with Down syndrome are classified as myeloid leukemia associated with Down syndrome.4

Down Syndrome Transient Abnormal Myelopoiesis(TAM), AML and how they may differentiate:

  • 5-10% of babies born with Down syndrome develop a transient form of leukemia that usually resolves on its own. This transient form is Transient Abnormal Myelopoiesis (TAM).2, 3
  • 20-30% of these babies with TAM progress to a more serious leukemia, usually a form of Acute Myeloid Leukemia within 1-4 years.3
  • In young children with Down Syndrome, Megakaryoblastic Leukemia (AML-M7) is the most common form of Leukemia.3
  • Some chromosomal abnormalities that have not been described in TAM. One of them is t (1; 22), which would be a differentiating factor for diagnosis of AML-M7 and TAM.3 Trisomy 21 is the recurrent chromosomal anomaly in both conditions. TAM may have cryptic inversions of chromosome 21 as opposed to interstitial deletions of 21q in acute leukemia’s.1
  • While the prognosis for AML is poor, with only a 35-60% survival rate, this is not the case for Down Syndrome patients suffering from AML.4
  • Bone marrow may have a lower blast count in TAM than in the peripheral smear than an AML.1, 3
  • Microarray transcript profiling is able to distinguish TAM from acute megakaryoblastic leukemia in patients with Down syndrome. Among the significant differences, CDKN2C, the effector of GATA1 -mediated cell cycle arrest, is increased in acute megakaryoblastic leukemia-but not in TAM, despite the similar level of GATA1.5


  1. Ketan P. Mallya, Deepak Nayak M., Sushma V. Belurkar , Chethan Manohar; TRANSIENT ABNORMAL MYELOPOIESIS IN A NEONATE,. January 2013.
  2. Alka V. Gosavi, Prashant S. Murarkar, Dhaneshwar N. Lanjewar, and Ravishankar V. Ravikar, Transient Leukemia in down Syndrome: Report of Two Cases with Review Literature; June 21, 2011.
  3. Dunphy, Cherie H; Pathology of Myeloid Proliferations Related to Down Syndrome. Medscape, June 05, 2013.
  4. Sekeres Mikkael, Acute Myeloid Leukemia, April 2014.
  5. McElwaine S, Mulligan C, Groet J, Spinelli M, Rinaldi A, Denyer G, et al. Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down’s syndrome, revealing PRAME as a specific discriminating marker. Br J Haematol. 2004 Jun. 125(6):729-42. [Medline].