Expression of megakaryocytic and myeloid markers in blasts of transient abnormal myelopoiesis in a stillbirth with Down syndrome: report of histopathological findings of an autopsy case

Ishigaki, Hirohito; Miyauchi, Jun; Yokoe, Akira; Nakayama, Misako; Yanagi, Takahide; Taga, Takashi; Ohta, Shigeru; Itoh, Yasushi; Ogasawara, Kunio

doi:10.1016/j.humpath.2010.06.012

Cited by 19 publications

(14 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in agreement with the present case, although intralobular diffuse liver fibrosis was present, myelofibrosis, a well-known complication of AMKL, is not detected in TAM [13]. TAM is distinct from AMKL in that TAM originates from the fetal liver while AMKL originates from the bone marrow several years after birth [8].…”

Section: Discussionsupporting

confidence: 90%

Hepatosplenomegaly Associated with Transient Abnormal Myelopoiesis in Down Syndrome: An Autopsy Case of a Stillborn Fetus

et al. 2015

View full text Add to dashboard Cite

A 38-year-old primiparous mother (gravida1, para 0) at 27 weeks and 6 days' gestation reported that fetal movements had been absent for 6 days. All serological markers for infection were negative. Chorionic villus sampling at stillbirth delivery revealed trisomy 21 (47, XX, +21), indicative of Down syndrome. The macerated baby was female and weighed 1,290 g. There was no evidence of hydrops fetalis. Proliferating blast cells expressing megakaryoblastic/megakaryocytic antigen CD61 were mainly seen within the vessels, and some cells infiltrated outside of the vessels in almost all organs. Vessels of the umbilical cord and chorionic villi were filled with proliferating blast cells, but the blast cells were not apparent in the bone marrow. The diagnosis of transient abnormal myelopoiesis in Down syndrome was made. Hepatomegaly (64.5 g) was due to congestion and infiltration of CD61-positive blast cells within the vascular lumina and expanding outside the lumina accompanied by fibrotic change. The cause of death was attributed to liver insufficiency caused by liver fibrosis. An umbilical cord and chorionic villi examination may be helpful in the diagnosis of transient abnormal myelopoiesis when post-mortem examination is not permitted.

show abstract

Section: Discussionsupporting

confidence: 90%

Hepatosplenomegaly Associated with Transient Abnormal Myelopoiesis in Down Syndrome: An Autopsy Case of a Stillborn Fetus

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Consistent with these in vitro data, massive increase of basophils in the peripheral blood of a patient with TL has been reported (Worth et al, 1999) and another case demonstrating pericardial effusion containing predominantly basophils has been described (Zipursky et al, 1997). We recently reported pathological findings on autopsy of a stillbirth with TL, in which numerous megakaryoblasts and dysplastic megakaryocytes were present in the liver and blood vessels, whereas leukemic blasts infiltrating into the peripheral tissues, including pericardium, expressed MPO (Ishigaki et al, 2011). These findings are consistent with the in vitro data described above and indicate that blasts in TL are not simply megakaryoblasts but derived from more primitive hematopoietic progenitors that are capable of differentiating into several myeloid lineages in vivo, possibly depending on the hematopoietic microenvironment.…”

Section: Differentiation Capability Of Leukemic Blastssupporting

confidence: 62%

“…Since blasts in TL have features similar to those of megakaryoblasts in AMKL-DS and TL is a disorder of neonates and fetuses, it appears that TL is a very unusual form of neoplasia originating from the fetal liver, the major organ of hematopoiesis during the fetal stage, and that leukemic blasts that arise in the fetal liver produce cytokines that stimulate fibroblasts to induce liver fibrosis in the same manner as myelofibrosis in AMKL-DS. Proliferation of dysplastic megakaryocytes and blasts, including megakaryoblasts, in the liver has been shown in autopsy cases of fetuses with TL (Ruchelli et al, 1991;Becroft, 1993;Ishigaki et al, 2011) and production of TGFβ by TL blasts in the liver has been immunohistochemically demonstrated (Arai et al, 1999). The presence of unique hematopoietic progenitors originating from the yolk sac and fetal liver that are sensitive to a b…”

Section: Origin Of Leukemic Progenitors and Association With Hematopomentioning

confidence: 99%

Unique Myeloid Leukemias in Young Children with Down Syndrome: Cell Origin, Association with Hematopoietic Microenvironment and Leukemogenesis

Miyauchi¹

2011

Prenatal Diagnosis and Screening for Down Syndrome

Self Cite

View full text Add to dashboard Cite

“…TAM can present as hydrops fetalis and hepatosplenomegaly in fetuses with DS . The most severe form of TAM is diagnosed on post‐mortem in stillborn DS fetuses . Infants with TAM may also have delayed‐onset hyperbilirubinemia, which is a sign of progressive liver fibrosis that can result in fatal liver failure .…”

Section: Clinical and Hematological Features Of Tammentioning

confidence: 99%

Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome

Watanabe

2019

Pediatrics International

View full text Add to dashboard Cite

Neonates with Down syndrome (DS) have a propensity to develop the unique myeloproliferative disorder, transient abnormal myelopoiesis (TAM). TAM usually resolves spontaneously in ≤3 months, but approximately 10% of patients with TAM die from hepatic or multi‐organ failure. After remission, 20% of patients with TAM develop acute myeloid leukemia associated with Down syndrome (ML‐DS). Blasts in both TAM and ML‐DS have trisomy 21 and GATA binding protein 1 (GATA1) mutations. Recent studies have shown that infants with DS and no clinical signs of TAM or increases in peripheral blood blasts can have minor clones carrying GATA1 mutations, referred to as silent TAM. Low‐dose cytarabine can improve the outcomes of patients with TAM and high white blood cell count. A number of studies using fetal liver cells, mouse models, or induced pluripotent stem cells have elucidated the roles of trisomy 21 and GATA1 mutations in the development of TAM. Next‐generation sequencing of TAM and ML‐DS patient samples identified additional mutations in genes involved in epigenetic regulation. Xenograft models of TAM demonstrate the genetic heterogeneity of TAM blasts and mimic the process of clonal selection and expansion of TAM clones that leads to ML‐DS. DNA methylation analysis suggests that epigenetic dysregulation may be involved in the progression from TAM to ML‐DS. Unraveling the mechanisms underlying leukemogenesis and identification of factors that predict progression to leukemia could assist in development of strategies to prevent progression to ML‐DS. Investigation of TAM, a unique pre‐leukemic condition, will continue to strongly influence basic and clinical research into the development of hematological malignancies.

show abstract

Expression of megakaryocytic and myeloid markers in blasts of transient abnormal myelopoiesis in a stillbirth with Down syndrome: report of histopathological findings of an autopsy case

Cited by 19 publications

References 13 publications

Hepatosplenomegaly Associated with Transient Abnormal Myelopoiesis in Down Syndrome: An Autopsy Case of a Stillborn Fetus

Hepatosplenomegaly Associated with Transient Abnormal Myelopoiesis in Down Syndrome: An Autopsy Case of a Stillborn Fetus

Unique Myeloid Leukemias in Young Children with Down Syndrome: Cell Origin, Association with Hematopoietic Microenvironment and Leukemogenesis

Recent advances in the understanding of transient abnormal myelopoiesis in Down syndrome

Contact Info

Product

Resources

About