Tetrasomy 21 transient leukemia with aGATA1 mutation in a phenotypically normal trisomy 21 mosaic infant: Case report and review of the literature

Abstract

Infants with constitutional trisomy 21 are at increased risk of developing transient and acute megakaryoblastic leukemia (AMKL). Mutations in GATA1 have been identified in trisomy 21 patients with AMKL, and this lesion is thought to be an initial event by virtue of its presence during transient leukemia. Transient leukemia is also observed in phenotypically normal infants albeit much less commonly so. Almost all these infants are mosaic for trisomy 21, and the clinical course of transient leukemia recapitulates that observed in constitutional trisomy 21. We report a phenotypically normal infant with tetrasomy 21 transient leukemia, GATA1 mutation within exon 2, and trisomy 21 mosaicism restricted to the hematopoietic tissue. Two years after diagnosis, low levels of trisomy 21 persisted in the peripheral blood, which resolved 2.5 years after diagnosis. The GATA1 mutation was not detected at last follow-up. The literature review identified 32 phenotypically normal infants with transient leukemia. Ninety-one percent (29 of 32) were observed and three received chemotherapy at diagnosis of transient leukemia. Nineteen percent (6 of 32) developed acute leukemia, and four continued in remission (two died). Transient leukemia in trisomy 21 mosaicism recapitulates the condition observed in constitutional trisomy 21 at the biological and clinical levels. Infants should be followed for the development of acute leukemia.

Mosaic Down syndrome-associated acute myeloid leukemia does not require high-dose cytarabine treatment for induction and consolidation therapy

“…Unfortunately, clinical samples were not obtained except UPN5; we could not reveal the correlation between the presence of GATA1 mutations and the good prognosis in our series. Sandoval et al [18] reported a patient of TAM with GATA1 mutation in a mosaic DS. The same interpretations would be made concerning GATA1 mutations in mosaic DS and AMKL.…”

Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome

“…[1][2][3] Children with DS have a 1 in 500 chance of developing acute megakaryoblastic leukemia (AMKL), 4-6 and 19% of DS (or trisomy 21 mosaic) neonates who are diagnosed with TL develop AMKL within 4 years. 3,7 Somatic mutations of GATA1 are found in almost all cases of DS or mosaic trisomy 21-associated TL and AMKL. 8 GATA1 mutations have not been detected in healthy children without DS, in DS children with other types of leukemia, or in AMKL cells of non-DS/non-trisomy 21 mosaic children, with the exception of a single case of adult AMKL without DS or acquired trisomy 21.…”

Transient abnormal myelopoiesis in a cytogenetically normal neonate

“…These cases highlight the significance of trisomy 21 as the causative cytogenetic alteration. However, genetic status of GATA1 has been rarely characterized and five such cases have been reported [8][9][10][11][12]. This patient showed G-C substitution in the boundary between exon 2 and intron 2 of GATA1.…”

“…In such cases, the status of GATA1 has been rarely characterized [8][9][10][11][12]. We present a cytogenetically normal neonate with TAM who showed acquired trisomy 21 and somatic mutation of GATA1 exon 2.…”