Clinical, cytogenetic, and molecular analyses of 17 neonates with transient abnormal myelopoiesis and nonconstitutional trisomy 21

Abstract

Background Transient abnormal myelopoiesis (TAM) is a unique myeloproliferative disorder that occurs in neonates with constitutional trisomy 21/Down syndrome (DS). Although TAM also develops in neonates without constitutional trisomy 21, the clinical, cytogenetic, and molecular characteristics of those patients are not fully understood. Procedure We retrospectively evaluated the clinical and cytogenetic findings and GATA1 mutation status of 17 neonates with TAM and nonconstitutional trisomy 21 tested for GATA1 mutations at our institute, and compared the findings with those of 64 neonates with TAM and constitutional trisomy 21/DS. Results DS clinical features were observed in five of the 17 (29%) patients. In all patients, both trisomy 21 and GATA1 mutations were detected in diagnostic samples. Over a median follow‐up of 33 (range, 0‐139) months, early death (< 6 months of age) occurred in four patients (24%). Overall and event‐free survivals were not significantly different between the patients with TAM and nonconstitutional trisomy 21 and those with TAM and constitutional trisomy 21/DS (five‐year overall survival: 76% ± 10% vs 53% ± 13%, P = 0.40; five‐year event‐free survival: 55% ± 13% vs 48% ± 12%, P = 0.90). The five‐year cumulative incidence of progression to myeloid leukemia of DS was also similar between the groups (21% vs 24%, P = 0.80). Conclusions Patients with TAM and nonconstitutional trisomy 21 exhibited similar biology and outcomes to those with TAM and constitutional trisomy 21/DS. The possibility of TAM should be considered even in phenotypically normal neonates with TAM symptoms, for appropriate management.

Comment on: Clinical, cytogenetic, and molecular analyses of 17 neonates with transient abnormal myelopoiesis and nonconstitutional trisomy 21

“…We observed a reduction of the blast count to 2% in the bone marrow aspiration 1 month after cessation of chemotherapy, along with dysplastic megakaryocytes with a karyotype analysis of 46, XX, and the disappearance of trisomy 21. The patient is under close follow‐up for overt leukemia, as suggested previously 1 …”

“…To the Editor: We are writing regarding the recent research entitled “Clinical, cytogenetic, and molecular analyses of 17 neonates with transient abnormal myelopoiesis and nonconstitutional trisomy 21” by Yuzawa et al 1 …”

Advances in molecular characterization of myeloid proliferations associated with Down syndrome

“…TAM is extremely rare in neonates without DS but such cases have been well documented ( Apollonsky et al, 2008 ; Tsai et al, 2011 ; Ono et al, 2015 ; Yuzawa et al, 2020 ; Panferova et al, 2021 ). The molecular pathogenesis and clinical outcomes of TAM in neonates without DS are similar to those with DS (i.e., DS-like).…”

“…In addition, GATA1 mutations may be germline, as recently reported in familial childhood cases of TAM/AMKL, highlighting a unique functional cooperation between these lesions that may be independent of the order of their acquisition ( Hasle et al, 2022 ). The rates of early death and leukemic progression of TAM in non-DS and DS children are similar, emphasizing the importance of making the diagnosis of DS-like TAM to assist appropriate patient management ( Yuzawa et al, 2020 ). Rare cases of TAM without GATA1 mutations feature in the literature.…”

“…The molecular pathogenesis and clinical outcomes of TAM in neonates without DS are similar to those with DS (i.e., DS-like). These patients acquire trisomy 21 and GATA1 mutations in the TAM clone ( Yuzawa et al, 2020 ; Panferova et al, 2021 ). In addition, GATA1 mutations may be germline, as recently reported in familial childhood cases of TAM/AMKL, highlighting a unique functional cooperation between these lesions that may be independent of the order of their acquisition ( Hasle et al, 2022 ).…”