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Acute megakaryoblastic leukemia with acquired trisomy 21 and GATA1 mutations in phenotypically normal children

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Abstract

GATA1 mutations are found almost exclusively in children with myeloid proliferations related to Down syndrome (DS). Here, we report two phenotypically and cytogenetically normal children with acute megakaryoblastic leukemia (AMKL) whose blasts had both acquired trisomy 21 and GATA1 mutation. Patient 1 was diagnosed with transient abnormal myelopoiesis in the neonatal period. Following spontaneous improvement of the disease, leukemic blasts increased 7 months later. He received less intensive chemotherapy, and he is now 6 years old in complete remission. Patient 2 was diagnosed with AMKL at the age of 18 months. Although he received intensive chemotherapy and a cord blood transplantation, he died without gaining remission. In both cases, trisomy 21 and GATA1 mutation were detected only in leukemic blasts, but not in germline samples. Based on a literature review, we identified reports describing 14 non-DS AMKL with GATA1 mutation and acquired trisomy 21. Of those, 12 cases were diagnosed during the neonatal period, whereas the remaining 2 cases were diagnosed at the age of 22 and 31 months, respectively.

Conclusion: These cases suggest that GATA1 mutation may cooperate with the additional chromosome 21 in developing myeloid proliferations even in non-DS patients.

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Abbreviations

AMKL:

Acute megakaryoblastic leukemia

BMA:

Bone marrow aspiration

CBC:

Complete blood count

CBT:

Cord blood transplantation

DS:

Down syndrome

FCM:

Flow cytometry

FISH:

Fluorescent in situ hybridization

ML-DS:

Myeloid leukemia associated with DS

PB:

Peripheral blood

PHA:

Phytohemagglutinin

TAM:

Transient abnormal myelopoiesis

UPN:

Unique patient number

WHO:

World Health Organization

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Correspondence to Daisuke Hasegawa.

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Communicated by David Nadal

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Ono, R., Hasegawa, D., Hirabayashi, S. et al. Acute megakaryoblastic leukemia with acquired trisomy 21 and GATA1 mutations in phenotypically normal children. Eur J Pediatr 174, 525–531 (2015). https://doi.org/10.1007/s00431-014-2430-3

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  • DOI: https://doi.org/10.1007/s00431-014-2430-3

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